The DOI matches its Crossref record; 113 of the 113 references it cites were found in a registry or an index; 3 of the 109 sources its claims cite were checked for support.
Cytokine Storm
Open accessAbstract
Cardiac disorders CTCAE Term Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 Pericarditis Asymptomatic, ECG or physical findings (e.g., rub) consistent with pericarditis Definition: A disorder characterized by flaky and dull skin; the pores are generally fine, the texture is a papery thin texture.
Overview
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Written from the paper’s full text.
TL;DR
This review proposes a unifying definition of cytokine storm as elevated circulating cytokine levels, acute systemic inflammatory symptoms, and secondary organ dysfunction beyond a normal pathogen response (or cytokine-driven organ dysfunction if no pathogen is present). It synthesizes mechanisms, causes, and treatments across iatrogenic, pathogen-induced, neoplastic/autoimmune/monogenic, and Covid-19-associated cytokine storm.
Key findings
- The authors propose three criteria for cytokine storm: elevated circulating cytokine levels, acute systemic inflammatory symptoms, and either secondary organ dysfunction due to inflammation beyond that attributable to a normal pathogen response (if a pathogen is present) or any cytokine-driven organ dysfunction (if no pathogen is present). Improvement with cytokine neutralization or antiinflammatory agents further supports the classification.
- Key cytokines implicated include interferon-γ, interleukin-1, interleukin-6, TNF, and interleukin-18. Interleukin-6 is highly elevated in CAR T-cell therapy–induced cytokine storm and several other cytokine storm disorders; tocilizumab and siltuximab have shown effectiveness in HLH, idiopathic multicentric Castleman’s disease, and CAR T-cell–induced cytokine storm. Emapalumab was recently approved for primary HLH, and anakinra is effective in some forms of cytokine storm.
- Causes span iatrogenic triggers (CAR T cells, blinatumomab, TGN1412, rituximab, gene therapies, immune checkpoint inhibitors, cardiac-bypass surgery, allogeneic stem-cell transplantation), pathogens (sepsis, EBV/CMV-associated HLH, HHV-8–associated multicentric Castleman’s disease, influenza), monogenic/autoimmune disorders (primary HLH mutations in PRF1, UNC13D, STXBP1, RAB27A, STX11, SH2D1A, XIAP, NLRC4; autoinflammatory diseases), and Covid-19.
- In Covid-19, elevated cytokines include interleukin-1β, interleukin-6, IP-10, TNF, interferon-γ, MIP1α and MIP1β, and VEGF; higher interleukin-6 levels are strongly associated with shorter survival. Dexamethasone reduces mortality among the most severe cases with elevated CRP and supplemental oxygen requirements, whereas two large randomized controlled trials of anti–interleukin-6 receptor therapies did not show a survival benefit in hospitalized patients with Covid-19.
Methods
- Narrative review; no primary study design, sample, or statistical analysis is reported. The authors synthesize literature and propose a unifying definition and conceptual framework for staging, assessment, and treatment of cytokine storm.
- The review discusses pathophysiological features, clinical presentation, management, and iatrogenic, pathogen-induced, neoplasia-induced, monogenic, and Covid-19–associated causes. No systematic search strategy or meta-analysis is described.
Limitations
- Stated: no single definition of cytokine storm or cytokine release syndrome is widely accepted, and there is disagreement about how these disorders differ from an appropriate inflammatory response; the National Cancer Institute CTCAE definition is too broad, and the American Society for Transplantation and Cellular Therapy definition focuses too specifically on iatrogenic causes.
- Stated: the authors do not propose a specific threshold for cytokine elevations above normal or recommend specific cytokine panels or particular cytokines that must be elevated, given the lack of available evidence; they call for future systematic assessment by a multidisciplinary consortium.
- Stated and evident: mechanisms of Covid-19–associated cytokine storm remain unclear, including whether immune hyperactivity or failure to resolve inflammation underlies severe cases; as a narrative review, it provides no primary data, systematic search, or formal risk-of-bias assessment.
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Claims the paper makes
85 Not checked yet · 51 Own interpretation · 40 No basis given · 2 Partly supported · 1 Supported · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
In the paper
“The relative frequencies of circulating activated CD4+ and CD8+ T cells and plasmablasts are increased in Covid-19.92”
§ Cytokine Storm > Covid-19–Associated Cytokine Storm
What the sources say
- Supportedcites [92] Mathew D, Giles JR, Baxter AE, et al. Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications. Science 2020; 369(6508): eabc8511- eabc8511. 32669297 PMC7402624 source
The CD8 and CD4 T-cell activation sections report increased frequencies of activated cells in COVID-19 patients compared with controls (Figs. 2 and 3). The B-cell section reports often markedly increased frequencies of circulating plasmablasts (Fig. 4). The responses were heterogeneous: roughly one-third of patients did not show increased T-cell activation or plasmablast frequencies. (LLM, conf=0.90)
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- Supported
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In the paper
“reports of hemophagocytosis and elevated cytokine levels — as well as beneficial effects of immunosuppressant agents — in affected patients, particularly those who are the most severely ill, suggest that cytokine storm may contribute to the pathogenesis of Covid-19.87,88”
§ Cytokine Storm > Covid-19–Associated Cytokine Storm
What the sources say
- Not checked yetcites [87] Moore JB, June CH. Cytokine release syndrome in severe COVID-19. Science 2020; 368: 473- 474. 32303591 source
- Partly supportedcites [88] The RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19 — preliminary report. N Engl J Med. DOI: 10.1056/NEJMoa2021436. 32678530 PMC7383595 sourceExperimental — accuracy not yet measured
The introductory discussion (page unavailable) reports elevated inflammatory markers, including interleukin-1 and interleukin-6, in some patients with severe Covid-19. The Discussion (page unavailable) reports a mortality benefit from dexamethasone in patients receiving respiratory support and suggests immunopathological elements may dominate later illness. These passages support the proposed inflammatory contribution, but the paper does not report hemophagocytosis. (LLM, conf=0.86)
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In the paper
“Although the initial drivers may differ, late-stage clinical manifestations of cytokine storm converge and often overlap.”
§ Cytokine Storm > Clinical Features and Laboratory Abnormalities
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In the paper
“The laboratory findings in cytokine storm are variable and influenced by the underlying cause.”
§ Cytokine Storm > Clinical Features and Laboratory Abnormalities
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In the paper
“the line between a normal and a dysregulated response to a severe infection is blurry”
plain- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: The immune system is expected to recognize foreign invaders, respond proportionally to the pathogen burden, and then return to homeostasis.
In the paper
“Levels of serum cytokines — most prominently, interferon-γ — are often more elevated in patients with cytokine storm due to CAR T-cell therapy than in patients with sepsis-induced cytokine storm”
§ Cytokine Storm > Clinical Features and Laboratory Abnormalities
What the sources say
- Not checked yetcites [12] Diorio C, Shaw PA, Pequignot E, et al. Diagnostic biomarkers to differentiate sepsis from cytokine release syndrome in critically ill children. Blood Adv 2020; 4: 5174- 5183. 33095872 PMC7594400 source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The neurologic toxic effects are often delayed, developing several days after the onset of the cytokine storm.”
§ Cytokine Storm > Clinical Features and Laboratory Abnormalities
What the sources say
- Not checked yetcites [7] Lee DW, Santomasso BD, Locke FL, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant 2019; 25: 625- 638. 30592986 PMC12180426 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Prominent elevations in serum inflammatory cytokine levels, such as interferon-γ (or CXCL9 and CXCL10, chemokines induced by interferon-γ), interleukin-6, interleukin-10, and soluble interleukin-2 receptor alpha, a marker of T-cell activation, are usually present.”
§ Cytokine Storm > Clinical Features and Laboratory Abnormalities
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In the paper
“Highly elevated serum interleukin-6 levels are found in CAR T-cell therapy–induced cytokine storm and several other cytokine storm disorders.”
§ Cytokine Storm > Clinical Features and Laboratory Abnormalities
What the sources say
- Not checked yetcites [8] Grupp SA, Kalos M, Barrett D, et al. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med 2013; 368: 1509- 1518. 23527958 PMC4058440 source
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In the paper
“The onset and duration of cytokine storm vary, depending on the cause and treatments administered.”
§ Cytokine Storm > Clinical Features and Laboratory Abnormalities
What the sources say
- Not checked yetcites [7] Lee DW, Santomasso BD, Locke FL, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant 2019; 25: 625- 638. 30592986 PMC12180426 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Nearly all patients with cytokine storm are febrile”
§ Cytokine Storm > Clinical Features and Laboratory Abnormalities
What the sources say
- Not checked yetcites [8] Grupp SA, Kalos M, Barrett D, et al. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med 2013; 368: 1509- 1518. 23527958 PMC4058440 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The combination of renal dysfunction, endothelial-cell death, and acute-phase hypoalbuminemia can lead to capillary leak syndrome and anasarca”
§ Cytokine Storm > Clinical Features and Laboratory Abnormalities
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In the paper
“it is difficult to distinguish cytokine storm due to sepsis from cytokine storm due to CAR T-cell therapy on the basis of clinical features alone”
§ Cytokine Storm > Clinical Features and Laboratory Abnormalities
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In the paper
“who often have higher levels of circulating interleukin-1β, procalcitonin, and markers of endothelial damage”
§ Cytokine Storm > Clinical Features and Laboratory Abnormalities
What the sources say
- Not checked yetcites [12] Diorio C, Shaw PA, Pequignot E, et al. Diagnostic biomarkers to differentiate sepsis from cytokine release syndrome in critically ill children. Blood Adv 2020; 4: 5174- 5183. 33095872 PMC7594400 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The interdependence of these inflammatory mediators further complicates the distinction between a normal and a dysregulated response.”
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In the paper
“changes that are similar to those observed in patients with cancer who are treated with high-dose interleukin-2”
§ Cytokine Storm > Clinical Features and Laboratory Abnormalities
What the sources say
- Not checked yetcites [10] Schwartzentruber DJ. Guidelines for the safe administration of high-dose interleukin-2. J Immunother 2001; 24: 287- 293. 11565830 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Thus, combinations of assays to rule out infection and measure serum cytokines can help to identify the cause of the cytokine storm.”
§ Cytokine Storm > Clinical Features and Laboratory Abnormalities
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In the paper
“Innate cells that are most often implicated in the pathogenesis of cytokine storm include neutrophils, macrophages, and NK cells.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cell Types Involved in Cytokine Storm
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In the paper
“The excessive cytokine production leads to hyperinflammation and multiorgan failure.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm
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In the paper
“Immune hyperactivation in cytokine storm can occur as a result of inappropriate triggering or danger sensing, with a response initiated in the absence of a pathogen”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm
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In the paper
“Iatrogenic causes of cytokine storm involving excessive T-cell activation, such as CAR T-cell and anti-CD28 antibody therapy, point to the ability of activated T cells to initiate cytokine storm.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cell Types Involved in Cytokine Storm
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In the paper
“Hemophagocytic macrophages are often observed in bone marrow biopsy specimens from patients with cytokine storm.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cell Types Involved in Cytokine Storm
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In the paper
“Impaired granule-mediated killing of infected cells or tumor cells by CTLs is a key aspect of some forms of cytokine storm.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cell Types Involved in Cytokine Storm
What the sources say
- Not checked yetcites [20] Crayne CB, Albeituni S, Nichols KE, Cron RQ. The immunology of macrophage activation syndrome. Front Immunol 2019; 10: 119- 119. 30774631 PMC6367262 source
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In the paper
“Serum biomarkers, including glycoprotein 130 (gp130), interferon-γ, and interleukin-1–receptor antagonist (IL1RA), can be used to predict the severity of cytokine storm induced by CAR T-cell therapy”
§ Cytokine Storm > Clinical Features and Laboratory Abnormalities
What the sources say
- Not checked yetcites [13] Teachey DT, Lacey SF, Shaw PA, et al. Identification of predictive biomarkers for cytokine release syndrome after chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia. Cancer Discov 2016; 6: 664- 679. 27076371 PMC5448406 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Thus, an exuberant inflammatory response to a large pathogen burden may be appropriate for controlling the infection if excessive secondary organ dysfunction does not occur”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm
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In the paper
“Data from mouse models of HLH and patients with cytokine storm indicate that the inability of CTLs to kill efficiently leads to prolonged activation of T cells, triggering a cascade of inflammatory tissue damage.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cell Types Involved in Cytokine Storm
What the sources say
- Not checked yetcites [21] Jordan MB, Hildeman D, Kappler J, Marrack P. An animal model of hemophagocytic lymphohistiocytosis (HLH): CD8+ T cells and interferon gamma are essential for the disorder. Blood 2004; 104: 735- 743. 15069016 source
- Not checked yetcites [22] Zhang K, Jordan MB, Marsh RA, et al. Hypomorphic mutations in PRF1, MUNC13-4, and STXBP2 are associated with adult-onset familial HLH. Blood 2011; 118: 5794- 5798. 21881043 PMC3228496 source
- Not checked yetcites [23] Schulert GS, Cron RQ. The genetics of macrophage activation syndrome. Genes Immun 2020; 21: 169- 181. 32291394 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“or failure to resolve the immune response and return to homeostasis (e.g., in primary HLH)”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm
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In the paper
“The grading systems used to predict and assess the severity of cytokine storm differ according to the cause.”
§ Cytokine Storm > Clinical Features and Laboratory Abnormalities
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In the paper
“An exaggerated Th1-type inflammatory response often occurs during cytokine storm.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cell Types Involved in Cytokine Storm
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In the paper
“In each of these states, there is a failure of negative feedback mechanisms that are meant to prevent hyperinflammation and the overproduction of inflammatory cytokines and soluble mediators.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm
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In the paper
“An experimental model of macrophage activation syndrome (a form of secondary HLH) provides evidence that Th17 cells can be drivers of a cytokine storm that is independent of interferon-γ.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cell Types Involved in Cytokine Storm
What the sources say
- Not checked yetcites [25] Avau A, Mitera T, Put S, et al. Systemic juvenile idiopathic arthritis-like syndrome in mice following stimulation of the immune system with Freund’s complete adjuvant: regulation by interferon-γ. Arthritis Rheumatol 2014; 66: 1340- 1351. 24470407 source
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In the paper
“Downstream signal transduction is mediated by JAKs (Janus kinases) and STAT3 (signal transducer and activator of transcription 3), as well as by Akt–mTOR (mammalian target of rapamycin) and MAPK–ERK (mitogen-activated protein kinase–extracellular signal-regulated kinase) pathways.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
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In the paper
“The administration of recombinant cytokines (e.g., interleukin-1, interleukin-6, interleukin-12, interleukin-18, tumor necrosis factor [TNF], and interferon-γ) in animal models and for cancer treatment in humans induces severe toxic effects or lethality consistent with the central role of cytokines as mediators of hyperinflammation in cytokine storm.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
What the sources say
- Not checked yetcites [27] Doherty GM, Lange JR, Langstein HN, Alexander HR, Buresh CM, Norton JA. Evidence for IFN-gamma as a mediator of the lethality of endotoxin and tumor necrosis factor-alpha. J Immunol 1992; 149: 1666- 1670. 1506688 source
- Not checked yetcites [28] Cohen J. IL-12 deaths: explanation and a puzzle. Science 1995; 270: 908- 908. 7481785 source
- Not checked yetcites [29] Atkins MB. Interleukin-2: clinical applications. Semin Oncol 2002; 29: Suppl 7: 12- 17. 12068383 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Levels of interleukin-6, an important mediator of the acute inflammatory response and pathophysiological features of cytokine storm, are highly elevated across various underlying immunopathologic disorders35,36 and in mouse models of cytokine storm.37”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
What the sources say
- Not checked yetcites [35] Winkler U, Jensen M, Manzke O, Schulz H, Diehl V, Engert A. Cytokine-release syndrome in patients with B-cell chronic lymphocytic leukemia and high lymphocyte counts after treatment with an anti-CD20 monoclonal antibody (rituximab, IDEC-C2B8). Blood 1999; 94: 2217- 2224. 10498591 source
- Not checked yetcites [36] Teachey DT, Rheingold SR, Maude SL, et al. Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy. Blood 2013; 121: 5154- 5157. 23678006 PMC4123427 source
- Not checked yetcites [37] van der Stegen SJ, Davies DM, Wilkie S, et al. Preclinical in vivo modeling of cytokine release syndrome induced by ErbB-retargeted human T cells: identifying a window of therapeutic opportunity? J Immunol 2013; 191: 4589- 4598. 24062490 source
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In the paper
“The pattern of cytokine elevations varies on the basis of such factors as the microbiome, genetic features, and underlying disorders.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
What the sources say
- Not checked yetcites [30] Schulert GS, Zhang M, Fall N, et al. Whole-exome sequencing reveals mutations in genes linked to hemophagocytic lymphohistiocytosis and macrophage activation syndrome in fatal cases of H1N1 influenza. J Infect Dis 2016; 213: 1180- 1188. 26597256 PMC4779301 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Activation of cis signaling results in pleiotropic effects on the immune system, which can contribute to cytokine storm.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
What the sources say
- Not checked yetcites [38] Kang S, Tanaka T, Narazaki M, Kishimoto T. Targeting interleukin-6 signaling in clinic. Immunity 2019; 50: 1007- 1023. 30995492 source
plainconditional- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
In the paper
“Both tocilizumab, a monoclonal antibody directed at the interleukin-6 receptor (interleukin-6R), and siltuximab, which neutralizes interleukin-6 directly, have been shown to be effective in a number of cytokine storm disorders, including HLH, idiopathic multicentric Castleman’s disease, and CAR T-cell–induced cytokine storm.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
What the sources say
- Not checked yetcites [38] Kang S, Tanaka T, Narazaki M, Kishimoto T. Targeting interleukin-6 signaling in clinic. Immunity 2019; 50: 1007- 1023. 30995492 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Conversely, reduction in symptoms and improvement in organ function with neutralization of specific cytokines with monoclonal antibodies also reveal that excessive levels of certain cytokines play a critical role in a number of cytokine storm disorders.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, the effectiveness of B-cell depletion in treating some cytokine storm disorders, such as human herpesvirus 8 (HHV-8)–associated multicentric Castleman’s disease, suggests that these cells are capable of initiating or propagating cytokine storm, particularly when virally infected.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cell Types Involved in Cytokine Storm
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In mouse models of toxic shock, TNF is the cytokine driver of superantigen-driven cytokine storm.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
What the sources say
- Not checked yetcites [39] Faulkner L, Cooper A, Fantino C, Altmann DM, Sriskandan S. The mechanism of superantigen-mediated toxic shock: not a simple Th1 cytokine storm. J Immunol 2005; 175: 6870- 6877. 16272345 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Interleukin-18 and interleukin-1β are activated from precursors by inflammasomes.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Patients with cytokine storm due to macrophage activation syndrome have high levels of interleukin-18 in serum,44”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
What the sources say
- Not checked yetcites [44] Mazodier K, Marin V, Novick D, et al. Severe imbalance of IL-18/IL-18BP in patients with secondary hemophagocytic syndrome. Blood 2005; 106: 3483- 3489. 16020503 PMC1895045 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The proinflammatory effects of interleukin-18 are normally kept in check by the interleukin-18–binding protein (IL18BP), which prevents the binding of interleukin-18 to its receptor.46”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
What the sources say
- Not checked yetcites [46] Dinarello CA, Novick D, Kim S, Kaplanski G. Interleukin-18 and IL-18 binding protein. Front Immunol 2013; 4: 289- 289. 24115947 PMC3792554 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Macrophages and dendritic cells are the primary sources of bioactive interleukin-18, which has many proinflammatory effects.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The resultant interleukin-6–soluble interleukin-6R–gp130–JAK-STAT3 signaling is then activated in cells that do not express the membrane-bound interleukin-6R, such as endothelial cells.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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In the paper
“Interleukin-1β and interleukin-18 are also potent inducers of interleukin-6 secretion from macrophages.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
What the sources say
- Not checked yetcites [43] Netea MG, Kullberg BJ, Verschueren I, Van Der Meer JW. Interleukin-18 induces production of proinflammatory cytokines in mice: no intermediate role for the cytokines of the tumor necrosis factor family and interleukin-1beta. Eur J Immunol 2000; 30: 3057- 3060. 11069090
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“In the presence of high circulating levels of interleukin-6, which can be present in cytokine storm, trans signaling occurs through the binding of interleukin-6 to the soluble form of interleukin-6R, forming a complex with a gp130 dimer on potentially all cell surfaces.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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In the paper
“In this disorder, uncontrolled infection with HHV-8 (also known as Kaposi’s sarcoma herpesvirus) leads to a cytokine storm driven primarily by excessive production of human interleukin-6 and viral interleukin-6 by HHV-8–infected plasmablasts.68”
§ Cytokine Storm > Pathogen-Induced Cytokine Storm
What the sources say
- Not checked yetcites [68] Polizzotto MN, Uldrick TS, Wang V, et al. Human and viral interleukin-6 and other cytokines in Kaposi sarcoma herpesvirus-associated multicentric Castleman disease. Blood 2013; 122: 4189- 4198. 24174627 PMC3868925 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Though interleukin-10 and IL1RA are often elevated in cytokine storm, this finding most likely reflects a secondary, albeit insufficient, counterregulatory response to the proinflammatory cytokines.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Furthermore, retrospective analyses of data from persons who died from coagulopathies and hemophagocytosis during the H1N1 influenza pandemic of 2009 revealed germline mutations previously associated with HLH-associated cytokine storm.30”
§ Cytokine Storm > Pathogen-Induced Cytokine Storm
What the sources say
- Not checked yetcites [30] Schulert GS, Zhang M, Fall N, et al. Whole-exome sequencing reveals mutations in genes linked to hemophagocytic lymphohistiocytosis and macrophage activation syndrome in fatal cases of H1N1 influenza. J Infect Dis 2016; 213: 1180- 1188. 26597256 PMC4779301 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Furthermore, in mice lacking interleukin-10, infection leads to cytokine storm.48”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
What the sources say
- Not checked yetcites [48] Behrens EM, Canna SW, Slade K, et al. Repeated TLR9 stimulation results in macrophage activation syndrome-like disease in mice. J Clin Invest 2011; 121: 2264- 2277. 21576823 PMC3104738 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“For example, reanalysis of a negative trial of interleukin-1β blockade in patients with sepsis identified a subgroup of patients with elevated ferritin levels who seemed to benefit from the treatment.63”
§ Cytokine Storm > Pathogen-Induced Cytokine Storm
What the sources say
- Not checked yetcites [63] Shakoory B, Carcillo JA, Chatham WW, et al. Interleukin-1 receptor blockade is associated with reduced mortality in sepsis patients with features of macrophage activation syndrome: reanalysis of a prior phase III trial. Crit Care Med 2016; 44: 275- 281. 26584195 PMC5378312 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Tumor lysis most likely also contributes to the cytokine storm through the induction of pyroptosis in target cells.55”
§ Cytokine Storm > Iatrogenic Cytokine Storm
What the sources say
- Not checked yetcites [55] Liu Y, Fang Y, Chen X, et al. Gasdermin E-mediated target cell pyroptosis by CAR T cells triggers cytokine release syndrome. Sci Immunol 2020; 5(43): eaax7969- eaax7969. 31953257 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“The ratio of free interleukin-18 to bound interleukin-18–IL18BP complexes in serum is an important indicator of the severity of the macrophage activation syndrome.44,47”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
What the sources say
- Not checked yetcites [44] Mazodier K, Marin V, Novick D, et al. Severe imbalance of IL-18/IL-18BP in patients with secondary hemophagocytic syndrome. Blood 2005; 106: 3483- 3489. 16020503 PMC1895045 source
- Not checked yetcites [47] Novick D, Kim S, Kaplanski G, Dinarello CA. Interleukin-18, more than a Th1 cytokine. Semin Immunol 2013; 25: 439- 448. 24275602 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“However, cytokine storm does not develop in all patients treated with CAR T cells or blinatumomab, so additional factors, such as CAR structure and design,51 disease burden,58 and host genomic background,59 are likely to play a part.”
§ Cytokine Storm > Iatrogenic Cytokine Storm
What the sources say
- Not checked yetcites [51] Xu XJ, Tang YM. Cytokine release syndrome in cancer immunotherapy with chimeric antigen receptor engineered T cells. Cancer Lett 2014; 343: 172- 178. 24141191 source
- Not checked yetcites [58] Frey NV, Porter DL. Cytokine release syndrome with novel therapeutics for acute lymphoblastic leukemia. Hematology Am Soc Hematol Educ Program 2016; 2016: 567- 572. 27913530 PMC6142489 source
- Not checked yetcites [59] Dahmer MK, Randolph A, Vitali S, Quasney MW. Genetic polymorphisms in sepsis. Pediatr Crit Care Med 2005; 6: Suppl: S61- S73. 15857562 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The administration of monoclonal antibodies directed at specific cytokines and the use of apheresis or medical devices to remove cytokines from circulation have had generally disappointing results in clinical trials.62”
§ Cytokine Storm > Pathogen-Induced Cytokine Storm
What the sources say
- Not checked yetcites [62] Fisher CJ Jr, Dhainaut JF, Opal SM, et al. Recombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome: results from a randomized, double-blind, placebo-controlled trial. JAMA 1994; 271: 1836- 1843. 8196140 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The highly activated CAR T cells are clearly the initiators of the cytokine storm.”
§ Cytokine Storm > Iatrogenic Cytokine Storm
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Hypocomplementemia, resulting from increased consumption by immune complexes, can be observed in cytokine storm.49”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
What the sources say
- Not checked yetcites [49] Gorelik M, Torok KS, Kietz DA, Hirsch R. Hypocomplementemia associated with macrophage activation syndrome in systemic juvenile idiopathic arthritis and adult onset Still’s disease: 3 cases. J Rheumatol 2011; 38: 396- 397. 21285182 PMC3672253 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Infusion of CAR T cells engineered to recognize and eliminate CD19+ lymphoma cells can induce cytokine storm, with supraphysiologic levels of interferon-γ and interleukin-6.50”
§ Cytokine Storm > Iatrogenic Cytokine Storm
What the sources say
- Not checked yetcites [50] Porter DL, Hwang WT, Frey NV, et al. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med 2015; 7: 303ra139- 303ra139. 26333935 PMC5909068 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Cytokine storm can be observed with other T-cell–engaging immunotherapies as well, such as blinatumomab, a bispecific antibody that binds to CD19+ and CD3+ T cells.56”
§ Cytokine Storm > Iatrogenic Cytokine Storm
What the sources say
- Not checked yetcites [56] Topp MS, Gökbuget N, Stein AS, et al. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol 2015; 16: 57- 66. 25524800 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The unfortunate consequences of another T-cell–activating treatment with the anti-CD28 superagonist TGN1412 show that rapid activation of large numbers of T cells can result in severe cytokine storm within minutes after infusion.57”
§ Cytokine Storm > Iatrogenic Cytokine Storm
What the sources say
- Not checked yetcites [57] Suntharalingam G, Perry MR, Ward S, et al. Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N Engl J Med 2006; 355: 1018- 1028. 16908486 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Nonablative inhibition of T cells with cyclosporine can also be helpful.77”
§ Cytokine Storm > Monogenic or Autoimmune Cytokine Storm
What the sources say
- Not checked yetcites [77] Mouy R, Stephan JL, Pillet P, Haddad E, Hubert P, Prieur AM. Efficacy of cyclosporine A in the treatment of macrophage activation syndrome in juvenile arthritis: report of five cases. J Pediatr 1996; 129: 750- 754. 8917244 source
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“These findings have led to treatment with the mTORC1 inhibitor sirolimus in patients with idiopathic multicentric Castleman’s disease who do not have a response to anti–interleukin-6 therapy.85”
§ Cytokine Storm > Monogenic or Autoimmune Cytokine Storm
What the sources say
- Not checked yetcites [85] Fajgenbaum DC, Langan R-A, Sada Japp A, et al. Identifying and targeting pathogenic PI3K/AKT/mTOR signaling in IL-6-blockade-refractory idiopathic multicentric Castleman disease. J Clin Invest 2019; 129: 4451- 4463. 31408438 PMC6763254 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Patients with genetic immunodeficiency syndromes such as chronic granulomatous disease and STAT1 gain-of-function disease can, paradoxically, present with cytokine storm from overwhelming infections.78”
§ Cytokine Storm > Monogenic or Autoimmune Cytokine Storm
What the sources say
- Not checked yetcites [78] Faitelson Y, Grunebaum E. Hemophagocytic lymphohistiocytosis and primary immune deficiency disorders. Clin Immunol 2014; 155: 118- 125. 25241079 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“For some viral infections, treating patients with proinflammatory cytokines in the early stages of infection can help to control the virus before detrimental effects of the immune response occur.73”
§ Cytokine Storm > Pathogen-Induced Cytokine Storm
What the sources say
- Not checked yetcites [73] Grajales-Reyes GE, Colonna M. Interferon responses in viral pneumonias. Science 2020; 369: 626- 627. 32764056 source
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Laboratory test results reflecting hyperinflammation and tissue damage were found to predict worsening outcomes in Covid-19.93”
§ Cytokine Storm > Covid-19–Associated Cytokine Storm
What the sources say
- Not checked yetcites [93] Caricchio R, Gallucci M, Dass C, et al. Preliminary predictive criteria for COVID-19 cytokine storm. Ann Rheum Dis 2020 September 25 (Epub ahead of print). 32978237 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Cyclophosphamide and etoposide, which are broadly cytotoxic but particularly effective at eliminating activated CD8+ T cells, are often effective in patients with primary HLH, secondary HLH (including macrophage activation syndrome), and corresponding models.75”
§ Cytokine Storm > Monogenic or Autoimmune Cytokine Storm
What the sources say
- Not checked yetcites [75] Johnson TS, Terrell CE, Millen SH, Katz JD, Hildeman DA, Jordan MB. Etoposide selectively ablates activated T cells to control the immunoregulatory disorder hemophagocytic lymphohistiocytosis. J Immunol 2014; 192: 84- 91. 24259502 PMC4177106 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Patients with the thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly (TAFRO) subtype tend to have the most severe cytokine storm.79”
§ Cytokine Storm > Monogenic or Autoimmune Cytokine Storm
What the sources say
- Not checked yetcites [79] Iwaki N, Fajgenbaum DC, Nabel CS, et al. Clinicopathologic analysis of TAFRO syndrome demonstrates a distinct subtype of HHV-8-negative multicentric Castleman disease. Am J Hematol 2016; 91: 220- 226. 26805758 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In patients with primary HLH, various autosomal recessive monogenic abnormalities in granule-mediated cytotoxicity lead to cytokine storm.”
§ Cytokine Storm > Monogenic or Autoimmune Cytokine Storm
What the sources say
- Not checked yetcites [23] Schulert GS, Cron RQ. The genetics of macrophage activation syndrome. Genes Immun 2020; 21: 169- 181. 32291394 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although the cause is unknown, interleukin-6 is the driver of pathogenesis in a large portion of patients.”
§ Cytokine Storm > Monogenic or Autoimmune Cytokine Storm
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Common pathologic mutations include those occurring in PRF1, UNC13D, STXBP1, RAB27A, STX11, SH2D1A, XIAP, and NLRC4.23”
§ Cytokine Storm > Monogenic or Autoimmune Cytokine Storm
What the sources say
- Not checked yetcites [23] Schulert GS, Cron RQ. The genetics of macrophage activation syndrome. Genes Immun 2020; 21: 169- 181. 32291394 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Both siltuximab and tocilizumab have been shown to resolve disease flares and sustain remission in approximately one third to one half of patients.80”
§ Cytokine Storm > Monogenic or Autoimmune Cytokine Storm
What the sources say
- Not checked yetcites [80] Nishimoto N, Kanakura Y, Aozasa K, et al. Humanized anti-interleukin-6 receptor antibody treatment of multicentric Castleman disease. Blood 2005; 106: 2627- 2632. 15998837 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Higher interleukin-6 levels are strongly associated with shorter survival.91”
§ Cytokine Storm > Covid-19–Associated Cytokine Storm
What the sources say
- Not checked yetcites [91] Del Valle DM, Kim-Schulze S, Huang H-H, et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med 2020; 26: 1636- 1643. 32839624 PMC7869028 source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Serum cytokine levels that are elevated in patients with Covid-19–associated cytokine storm include interleukin-1β, interleukin-6, IP-10, TNF, interferon-γ, macrophage inflammatory protein (MIP) 1α and 1β, and VEGF.89,90”
§ Cytokine Storm > Covid-19–Associated Cytokine Storm
What the sources say
- Not checked yetcites [89] Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395: 497- 506. 31986264 PMC7159299 source
- Not checked yetcites [90] Zhu Z, Cai T, Fan L, et al. Clinical value of immune-inflammatory parameters to assess the severity of coronavirus disease 2019. Int J Infect Dis 2020; 95: 332- 339. 32334118 PMC7195003 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The beneficial effects of glucocorticoids, cyclosporine, anti–interleukin-1 antibody, JAK1 and JAK2 inhibitors, anti–interleukin-6 antibody, and cytotoxic chemotherapies in some patients with primary or secondary HLH suggest that pathways targeted by these agents are key to pathogenesis.”
§ Cytokine Storm > Monogenic or Autoimmune Cytokine Storm
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Other elevated serum cytokines and cellular signaling pathways that could be considered for therapeutic targeting include CXCL13, CXCL10 (interferon-inducible protein 10 [IP-10]), VEGF-A,82 type I interferon,83 mTOR complex 1 (mTORC1),84 and JAK-STAT3.”
§ Cytokine Storm > Monogenic or Autoimmune Cytokine Storm
What the sources say
- Not checked yetcites [82] Pierson SK, Stonestrom AJ, Shilling D, et al. Plasma proteomics identifies a ‘chemokine storm’ in idiopathic multicentric Castleman disease. Am J Hematol 2018; 93: 902- 912. 29675946 source
- Not checked yetcites [83] Langan Pai R-A, Sada Japp A, Gonzalez M, et al. Type I IFN response associated with mTOR activation in the TAFRO subtype of idiopathic multicentric Castleman disease. JCI Insight 2020; 5(9): e135031- e135031. 32376796 PMC7253017 source
- Not checked yetcites [84] Arenas DJ, Floess K, Kobrin D, et al. Increased mTOR activation in idiopathic multicentric Castleman disease. Blood 2020; 135: 1673- 1684. 32206779 PMC7205815 source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The correlation between the nasopharyngeal viral load and cytokine levels (e.g., interferon-α, interferon-γ, and TNF), as well as a declining viral load in moderate but not severe cases, suggests that the immune response is positively associated with the viral burden.26”
§ Cytokine Storm > Covid-19–Associated Cytokine Storm
What the sources say
- Not checked yetcites [26] Lucas C, Wong P, Klein J, et al. Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature 2020; 584: 463- 469. 32717743 PMC7477538 source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Neutralization of a particular cytokine whose level is elevated in the circulation with an existing agent (anti–interleukin-6, anti-TNF, anti–interferon-γ, or anti–interleukin-1β antibody) will not always be effective”
§ Cytokine Storm > Therapeutics
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Despite positive anecdotal reports, two large, randomized, controlled trials of anti–interleukin-6 receptor antibody therapies did not show a survival benefit in hospitalized patients with Covid-19.97,98”
§ Cytokine Storm > Covid-19–Associated Cytokine Storm
What the sources say
- Not checked yetcites [97] Hermine O, Mariette X, Tharaux PL, et al. Effect of tocilizumab vs usual care in adults hospitalized with COVID-19 and moderate or severe pneumonia: a randomized clinical trial. JAMA Intern Med 2020 October 20 (Epub ahead of print). 33080017 PMC7577198 source
- Not checked yetcites [98] Stone JH, Frigault MJ, Serling-Boyd NJ, et al. Efficacy of tocilizumab in patients hospitalized with Covid-19. N Engl J Med 2020 October 21 DOI: 10.1056/NEJMoa2028836. 33085857 PMC7646626 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Fourth, clotting issues can occur across cytokine storm disorders, but thromboembolic events appear to be more frequent in Covid-19–associated cytokine storm.99”
§ Cytokine Storm > Covid-19–Associated Cytokine Storm
What the sources say
- Not checked yetcites [99] Klok FA, Kruip MJHA, van der Meer NJM, et al. Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: an updated analysis. Thromb Res 2020; 191: 148- 150. 32381264 PMC7192101 source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“A study involving patients with systemic juvenile idiopathic arthritis revealed subgroups of patients with cytokine profiles in which interleukin-6 and interleukin-18 predominated, pointing toward available therapeutic approaches.110”
§ Cytokine Storm > Therapeutics
What the sources say
- Not checked yetcites [110] Shimizu M, Nakagishi Y, Yachie A. Distinct subsets of patients with systemic juvenile idiopathic arthritis based on their cytokine profiles. Cytokine 2013; 61: 345- 348. 23276493 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As with dexamethasone, the timing of treatment and selection of subgroups of patients included in studies will most likely have an effect on outcomes.”
§ Cytokine Storm > Covid-19–Associated Cytokine Storm
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The immune response to SARS-CoV-2 is critical for controlling viral replication and clearance.
None of the sources cited for this claim have been checked yet.
In the paper
“Alternatively, the discoveries of inborn errors of type I interferon immunity and autoantibodies against type I interferons in the most severe cases of Covid-19 suggest that an inadequate antiviral response may be contributory in some patients with Covid-19.94,95”
§ Cytokine Storm > Covid-19–Associated Cytokine Storm
What the sources say
- Not checked yetcites [94] Zhang Q, Bastard P, Liu Z, et al. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science 2020 September 24 (Epub ahead of print). 32972995 PMC7857407 source
- Not checked yetcites [95] Bastard P, Rosen LB, Zhang Q, et al. Auto-antibodies against type I IFNs in patients with life-threatening COVID-19. Science 2020 September 24 (Epub ahead of print). 32972996 PMC7857397 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“A meta-analysis of seven randomized trials showed that 28-day all-cause mortality in critically ill patients with Covid-19 was lower among those who were treated with glucocorticoids than among those who received usual care or placebo.100”
§ Cytokine Storm > Covid-19–Associated Cytokine Storm
What the sources say
- Not checked yetcites [100] Sterne JAC, Murthy S, Diaz JV, et al. Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis. JAMA 2020; 324: 1330- 1341. 32876694 PMC7489434 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Second, the primary site of infection and disease most likely contributes to differences in immune responses and mechanisms underlying the cytokine storm, which have implications for treatment.”
§ Cytokine Storm > Covid-19–Associated Cytokine Storm
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“JAK1 and JAK2 inhibitors, which are approved for the treatment of a number of autoimmune and neoplastic conditions, have the potential to inhibit signaling downstream of type I interferon, interleukin-6 (and other gp130 family receptors), interferon-γ, and interleukin-2, among other cytokines.107”
§ Cytokine Storm > Covid-19–Associated Cytokine Storm
What the sources say
- Not checked yetcites [107] Zhang W, Zhao Y, Zhang F, et al. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): the perspectives of clinical immunologists from China. Clin Immunol 2020; 214: 108393- 108393. 32222466 PMC7102614 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Likewise, biomarkers were recently shown to effectively predict which patients with adult-onset Still’s disease would have a response to anakinra or tocilizumab.111”
§ Cytokine Storm > Therapeutics
What the sources say
- Not checked yetcites [111] Vercruysse F, Barnetche T, Lazaro E, et al. Adult-onset Still’s disease biological treatment strategy may depend on the phenotypic dichotomy. Arthritis Res Ther 2019; 21: 53- 53. 30755262 PMC6373016 source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Much like anti–interleukin-6 antibody therapy, inhibition of Bruton tyrosine kinase and JAK could prove to be damaging or unhelpful if given too soon, when the immune response to SARS-CoV-2 is critical in controlling viral replication and clearance.”
§ Cytokine Storm > Covid-19–Associated Cytokine Storm
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The immune response to SARS-CoV-2 is critical for controlling viral replication and clearance.
None of the sources cited for this claim have been checked yet.
In the paper
“Further support comes from positive anecdotal reports of targeted antagonists against interleukin-1, granulocyte–macrophage colony-stimulating factor, and JAK1 and JAK2 in patients with Covid-19.102-105”
§ Cytokine Storm > Covid-19–Associated Cytokine Storm
What the sources say
- Not checked yetcites [102] Fajgenbaum DC, Khor JS, Gorzewski A, et al. Treatments administered to the first 9152 reported cases of COVID-19: a systematic review. Infect Dis Ther 2020; 9: 435- 449. 32462545 PMC7251321 source
- Not checked yetcites [103] De Luca G, Cavalli G, Campochiaro C, et al. GM-CSF blockade with mavrilimumab in severe COVID-19 pneumonia and systemic hyperinflammation: a single-centre, prospective cohort study. Lancet Rheumatol 2020; 2(8): e465- e473. 32835256 PMC7430344 source
- Not checked yetcites [104] Bronte V, Ugel S, Tinazzi E, et al. Baricitinib restrains the immune dysregulation in patients with severe COVID-19. J Clin Invest 2020 November 03 (Epub ahead of print). 32809969 PMC8016181 source
- Not checked yetcites [105] Rodriguez-Garcia JL, Sanchez-Nievas G, Arevalo-Serrano J, Garcia-Gomez C, Jimenez-Vizuete JM, Martinez-Alfaro E. Baricitinib improves respiratory function in patients treated with corticosteroids for SARS-CoV-2 pneumonia: an observational cohort study. Rheumatology (Oxford) 2020 October 06 (Epub ahead of print). 33020836 PMC7665718 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“immunosuppressive agents most likely increase the risk further.”
§ Cytokine Storm > Therapeutics
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 59
- Probably not a substantial claim. 52
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“As with EBV-associated HLH,71 rituximab is highly effective in patients with HHV-8–associated multicentric Castleman’s disease, since B-cell depletion removes the primary reservoir for HHV-8.72”
§ Cytokine Storm > Pathogen-Induced Cytokine Storm
What the sources say
- Partly supportedcites [71] Chellapandian D, Das R, Zelley K, et al. Treatment of Epstein Barr virus-induced haemophagocytic lymphohistiocytosis with rituximab-containing chemo-immunotherapeutic regimens. Br J Haematol 2013; 162: 376- 382. 23692048 PMC3776423 sourceExperimental — accuracy not yet measured
This source is citation 71, attached to the comparison with EBV-associated HLH; the HHV-8 claim has a separate citation. The Results report clinical improvement in 43% of patients receiving rituximab-containing regimens, but the Discussion says the retrospective study cannot determine rituximab’s efficacy on its own. It therefore does not support calling rituximab highly effective for EBV-associated HLH. (LLM, conf=0.86)
- Not checked yetcites [72] Dalla Pria A, Pinato D, Roe J, Naresh K, Nelson M, Bower M. Relapse of HHV8-positive multicentric Castleman disease following rituximab-based therapy in HIV-positive patients. Blood 2017; 129: 2143- 2147. 28143881 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“certain cytokines may be both helpful in controlling an infection and harmful to the host”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Many patients have hypertriglyceridemia and various blood-count abnormalities, such as leukocytosis, leukopenia, anemia, thrombocytopenia, and elevated ferritin and d-dimer levels.”
§ Cytokine Storm > Clinical Features and Laboratory Abnormalities
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These symptoms may be due directly to cytokine-induced tissue damage or acute-phase physiological changes or may result from immune-cell–mediated responses.”
§ Cytokine Storm > Clinical Features and Laboratory Abnormalities
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“No single definition of cytokine storm or the cytokine release syndrome is widely accepted”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In severe cases of cytokine storm, renal failure, acute liver injury or cholestasis, and a stress-related or takotsubo-like cardiomyopathy can also develop.”
§ Cytokine Storm > Clinical Features and Laboratory Abnormalities
What the sources say
- Not checked yetcites [9] Templin C, Ghadri JR, Diekmann J, et al. Clinical features and outcomes of takotsubo (stress) cardiomyopathy. N Engl J Med 2015; 373: 929- 938. 26332547 source
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“CAR T-cell therapy and other noninfectious causes can also occur with infections, and infections can develop during the course of therapy, so continued monitoring for infections is warranted.”
§ Cytokine Storm > Clinical Features and Laboratory Abnormalities
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Cytokine storm is an umbrella term encompassing several disorders of immune dysregulation characterized by constitutional symptoms, systemic inflammation, and multiorgan dysfunction that can lead to multiorgan failure if inadequately treated”
§ Cytokine Storm > Clinical Features and Laboratory Abnormalities
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“The National Cancer Institute’s definition, based on the Common Terminology Criteria for Adverse Events (CTCAE), is too broad, since the criteria for an inflammatory syndrome can also apply to other physiological states”
What the sources say
- Not checked yetcites [7] Lee DW, Santomasso BD, Locke FL, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant 2019; 25: 625- 638. 30592986 PMC12180426 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Changes in circulating cell counts are most likely due to a complex interplay among cytokine-induced changes in production and mobilization of cells from the bone marrow, immune-mediated destruction, and chemokine-induced migration.”
§ Cytokine Storm > Clinical Features and Laboratory Abnormalities
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The combination of hyperinflammation, coagulopathy, and low platelet counts places patients with cytokine storm at high risk for spontaneous hemorrhage.”
§ Cytokine Storm > Clinical Features and Laboratory Abnormalities
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“the definition of the American Society for Transplantation and Cellular Therapy is based on criteria that focus too specifically on iatrogenic causes of cytokine storm alone”
What the sources say
- Not checked yetcites [7] Lee DW, Santomasso BD, Locke FL, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant 2019; 25: 625- 638. 30592986 PMC12180426 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“there is disagreement about how these disorders differ from an appropriate inflammatory response”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Nonspecific markers of inflammation such as C-reactive protein (CRP) are universally elevated and correlate with severity.”
§ Cytokine Storm > Clinical Features and Laboratory Abnormalities
What the sources say
- Not checked yetcites [11] Lee DW, Gardner R, Porter DL, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood 2014; 124: 188- 195. 24876563 PMC4093680 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“patients may have fatigue, anorexia, headache, rash, diarrhea, arthralgia, myalgia, and neuropsychiatric findings”
§ Cytokine Storm > Clinical Features and Laboratory Abnormalities
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Disorders that should be ruled out in considering cytokine storm include anaphylaxis and physiological responses to microbial infections.”
§ Cytokine Storm > Clinical Features and Laboratory Abnormalities
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Cases can progress rapidly to disseminated intravascular coagulation with either vascular occlusion or catastrophic hemorrhages, dyspnea, hypoxemia, hypotension, hemostatic imbalance, vasodilatory shock, and death.”
§ Cytokine Storm > Clinical Features and Laboratory Abnormalities
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“the fever may be high grade in severe cases”
§ Cytokine Storm > Clinical Features and Laboratory Abnormalities
What the sources say
- Not checked yetcites [8] Grupp SA, Kalos M, Barrett D, et al. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med 2013; 368: 1509- 1518. 23527958 PMC4058440 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Cytokine storm and cytokine release syndrome are life-threatening systemic inflammatory syndromes involving elevated levels of circulating cytokines and immune-cell hyperactivation that can be triggered by various therapies, pathogens, cancers, autoimmune conditions, and monogenic disorders.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Many patients have respiratory symptoms, including cough and tachypnea, that can progress to acute respiratory distress syndrome (ARDS), with hypoxemia that may require mechanical ventilation.”
§ Cytokine Storm > Clinical Features and Laboratory Abnormalities
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Interferon-γ can induce hemophagocytosis by macrophages, and this may contribute to the cytopenias commonly observed in patients with cytokine storm.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cell Types Involved in Cytokine Storm
What the sources say
- Not checked yetcites [16] Zoller EE, Lykens JE, Terrell CE, et al. Hemophagocytosis causes a consumptive anemia of inflammation. J Exp Med 2011; 208: 1203- 1214. 21624938 PMC3173248 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“whereas similarly high levels of cytokines in cancer-associated HLH or idiopathic multicentric Castleman’s disease would be considered a pathologic state of cytokine storm because no pathogen requiring an immune response is involved and patients benefit from treatment with cytokine neutralization and other antiinflammatory agents.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“At increased levels, cytokines can have systemic effects and cause collateral damage to vital organ systems.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
In the paper
“Th17 cells have a major role in host defense, particularly antifungal protection, and abnormal Th17-cell function can lead to autoimmunity.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cell Types Involved in Cytokine Storm
What the sources say
- Not checked yetcites [24] Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 cells. Annu Rev Immunol 2009; 27: 485- 517. 19132915 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, lack of a treatment response does not necessarily rule out cytokine storm, because underlying conditions are likely to play a part, a different cytokine may be the disease driver, or the timing of treatment may have been poor.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Excess interleukin-6 may mediate the impairment in NK-cell function by lowering perforin and granzyme production.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cell Types Involved in Cytokine Storm
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Regulatory cell types, decoy receptors for proinflammatory cytokines such as IL1RA, and antiinflammatory cytokines such as interleukin-10 are important for antagonizing inflammatory-cell populations and preventing immune hyperactivity.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Neutrophils can produce neutrophil extracellular traps, a network of fibers that contribute to thrombi formation and amplify cytokine production during cytokine storm.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cell Types Involved in Cytokine Storm
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Cytokines play a key role in coordinating antimicrobial effector cells and providing regulatory signals that direct, amplify, and resolve the immune response.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“an inappropriate or ineffective amplitude of response, involving excessive effector immune-cell activation (e.g., in cytokine storm due to CAR T-cell therapy), an overwhelming pathogen burden (e.g., in sepsis), or uncontrolled infections and prolonged immune activation”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“For the grading of cytokine storm due to other causes, the immune systems disorders section of CTCAE is used”
§ Cytokine Storm > Clinical Features and Laboratory Abnormalities
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“HScore and MS score are used for classifying HLH-associated cytokine storm, and HLH-2004 guides treatment.”
§ Cytokine Storm > Clinical Features and Laboratory Abnormalities
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Circulating cytokine levels can be difficult to measure because cytokines have short half-lives, circulating levels may not accurately reflect local tissue levels, and measurements may not be easily obtained worldwide.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
- Rests on an assumption: Cytokines have short half-lives, which normally prevents them from having effects outside lymphoid tissue and sites of inflammation.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Inflammation involves a set of biologic mechanisms that evolved in multicellular organisms to contain invasive pathogens and resolve injuries by activating innate and adaptive immune responses.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In short, cytokine storm involves an immune response that causes collateral damage, which may be greater than the immediate benefit of the immune response.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Rests on an assumption: The immune system is expected to recognize foreign invaders, respond proportionally to the pathogen burden, and then return to homeostasis.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Improvement in outcomes with cytokine neutralization or antiinflammatory agents further supports the pathologic role of excessive cytokines and the classification of a condition as a cytokine storm.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“Th1 cells produce large quantities of interferon-γ, induce delayed hypersensitivity reactions, activate macrophages, and are essential for defense against intracellular pathogens.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cell Types Involved in Cytokine Storm
What the sources say
- Not checked yetcites [19] Mosmann TR, Coffman RL. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 1989; 7: 145- 173. 2523712 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This response requires a balance between sufficient cytokine production to eliminate the pathogen and avoidance of a hyperinflammatory response in which an overabundance of cytokines causes clinically significant collateral damage.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Rests on an assumption: The immune system is expected to recognize foreign invaders, respond proportionally to the pathogen burden, and then return to homeostasis.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although typically considered to be pathologic, sustained production of cytokines that leads to elevated circulating levels may be necessary to appropriately control some disseminated infections.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In many forms of cytokine storm, macrophages become activated and secrete excessive amounts of cytokines, ultimately causing severe tissue damage that can lead to organ failure.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cell Types Involved in Cytokine Storm
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The cytolytic function of NK cells is diminished in some forms of cytokine storm, which can lead to prolonged antigenic stimulation and difficulty resolving inflammation.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cell Types Involved in Cytokine Storm
What the sources say
- Not checked yetcites [17] Perez N, Virelizier J-L, Arenzana-Seisdedos F, Fischer A, Griscelli C. Impaired natural killer activity in lymphohistiocytosis syndrome. J Pediatr 1984; 104: 569- 573. 6368780 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Interleukin-1 is encoded by two genes (IL1A and IL1B), both of which bind to the same interleukin-1 receptor, activating a cascade of intracellular signaling pathways, including nuclear factor κB (NF-κB).”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The interleukin-1–receptor antagonist anakinra is effective as a single agent and in combination with other agents for the treatment of some forms of cytokine storm.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
What the sources say
- Not checked yetcites [33] Eloseily EM, Weiser P, Crayne CB, et al. Benefit of anakinra in treating pediatric secondary hemophagocytic lymphohistiocytosis. Arthritis Rheumatol 2020; 72: 326- 334. 31513353 source
- Not checked yetcites [34] Durand M, Troyanov Y, Laflamme P, Gregoire G. Macrophage activation syndrome treated with anakinra. J Rheumatol 2010; 37: 879- 880. 20360206 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Interleukin-6 is one of the more complex cytokines, since it is produced by and acts on immune and nonimmune cells across multiple organ systems.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Interferon-γ, interleukin-1, interleukin-6, TNF, and interleukin-18 are key cytokines that often have elevated levels in cytokine storm and are thought to have central immunopathologic roles.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Interferon-γ is primarily secreted by activated T cells and NK cells and is a potent activator of macrophages.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Membrane-bound gp130 is ubiquitously expressed, whereas expression of membrane-bound interleukin-6R is restricted largely to immune cells.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“B cells are not often associated with the pathogenesis of cytokine storm.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cell Types Involved in Cytokine Storm
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“Emapalumab, a monoclonal antibody that binds interferon-γ, was recently approved for the treatment of cytokine storm in patients with primary HLH.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
What the sources say
- Not checked yetcites [32] Locatelli F, Jordan MB, Allen C, et al. Emapalumab in children with primary hemophagocytic lymphohistiocytosis. N Engl J Med 2020; 382: 1811- 1822. 32374962 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Fever, a clinical hallmark of cytokine storm, can be elicited by interleukin-1, interleukin-6, or TNF through distinct mechanisms.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The specific immune cells that secrete the various cytokines are not fully understood and most likely vary among cytokine storm disorders.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“Clinically, interferon-γ causes fever, chills, headache, dizziness, and fatigue.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
What the sources say
- Not checked yetcites [31] Vadhan-Raj S, Nathan CF, Sherwin SA, Oettgen HF, Krown SE. Phase I trial of recombinant interferon gamma by 1-hour i.v. infusion. Cancer Treat Rep 1986; 70: 609- 614. 3085930
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In cis signaling, soluble interleukin-6 binds to membrane-bound interleukin-6R, forming an interleukin-6–interleukin-6R complex that binds to gp130, which then initiates signaling through its intracellular domain.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“It can signal through two main pathways, referred to as classic cis signaling and trans signaling.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
What the sources say
- Not checked yetcites [38] Kang S, Tanaka T, Narazaki M, Kishimoto T. Targeting interleukin-6 signaling in clinic. Immunity 2019; 50: 1007- 1023. 30995492 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The membrane-bound interleukin-6R does not possess intracellular signaling domains but signals instead through interaction with membrane-bound gp130.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This agent may also be useful in other cytokine storm disorders, such as macrophage activation syndrome or CAR T-cell–associated cytokine storm, although in the latter case, it may diminish antitumor effects.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In addition to inducing fever, augmenting systemic inflammation, and activating antimicrobial responses such as interleukin-6, TNF can induce cellular apoptosis and regulate immunity.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The interleukin-18 receptor is constitutively expressed on NK cells and induced on activation in most T cells.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“TNF and other cytokines in the TNF–TNF receptor superfamily are potent inducers of NF-κB, leading to the expression of multiple proinflammatory genes.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“This results in systemic hyperinflammation involving secretion of monocyte chemoattractant protein 1 (MCP-1), interleukin-8, and additional interleukin-6, as well as increased vascular endothelial growth factor (VEGF) and reduced E-cadherin expression on endothelial cells, which contribute to vascular hyperpermeability, leakiness, hypotension, and pulmonary dysfunction.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
What the sources say
- Not checked yetcites [38] Kang S, Tanaka T, Narazaki M, Kishimoto T. Targeting interleukin-6 signaling in clinic. Immunity 2019; 50: 1007- 1023. 30995492 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The effectiveness of anti-TNF therapies in certain autoinflammatory-driven cytokine storm conditions points to their potential role in the treatment of cytokine storm, but the limitations and dangers of anti-TNF therapies in patients with sepsis indicate that more work is needed.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The inflammasome is a multimolecular cytosolic sensor that detects pathogenic microorganisms and sterile stressors and activates caspase-1 during the process of pyroptosis, which, in turn, causes the inactive precursor forms of interleukin-1β and interleukin-18 to become the active forms.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
What the sources say
- Not checked yetcites [41] Martinon F, Pétrilli V, Mayor A, Tardivel A, Tschopp J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 2006; 440: 237- 241. 16407889 source
- Not checked yetcites [42] Frank D, Vince JE. Pyroptosis versus necroptosis: similarities, differences, and crosstalk. Cell Death Differ 2019; 26: 99- 114. 30341423 PMC6294779 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“interleukin-18 is a biomarker of severity that correlates with hyperferritinemia, elevated aminotransferase levels, and disease flare.45”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
What the sources say
- Not checked yetcites [45] Shimizu M, Yokoyama T, Yamada K, et al. Distinct cytokine profiles of systemic-onset juvenile idiopathic arthritis-associated macrophage activation syndrome with particular emphasis on the role of interleukin-18 in its pathogenesis. Rheumatology (Oxford) 2010; 49: 1645- 1653. 20472718 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Most important, it synergizes with interleukin-12 or interleukin-15 to stimulate secretion of interferon-γ from T cells and NK cells, and thus promotes Th1-type inflammatory responses.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“TNF is a potent, multifunctional, proinflammatory cytokine that belongs to the TNF–TNF receptor superfamily.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Interleukin-18 is a member of the large interleukin-1 family40 that has recently been associated with cytokine storm disorders.”
§ Cytokine Storm > Pathophysiological Features of Cytokine Storm > Cytokines
What the sources say
- Not checked yetcites [40] Garlanda C, Dinarello CA, Mantovani A. The interleukin-1 family: back to the future. Immunity 2013; 39: 1003- 1018. 24332029 PMC3933951 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“possibly because of lower interleukin-6 production by NK cells than by T cells and different cross-talk with myeloid cells.”
§ Cytokine Storm > Iatrogenic Cytokine Storm
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
In the paper
“In a recent study of NK-cell CAR therapy, there were no reported cases of cytokine storm or even elevated interleukin-6 levels,60”
§ Cytokine Storm > Iatrogenic Cytokine Storm
What the sources say
- Not checked yetcites [60] Liu E, Marin D, Banerjee P, et al. Use of CAR-transduced natural killer cells in CD19-positive lymphoid tumors. N Engl J Med 2020; 382: 545- 553. 32023374 PMC7101242 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Like CAR T cells, activated T cells initiate the cytokine storm, and macrophage activation propagates blinatumomab-induced cytokine storm, which also responds to anti–interleukin-6 antibody therapy.36”
§ Cytokine Storm > Iatrogenic Cytokine Storm
What the sources say
- Not checked yetcites [36] Teachey DT, Rheingold SR, Maude SL, et al. Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy. Blood 2013; 121: 5154- 5157. 23678006 PMC4123427 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“For example, patients lacking functional perforin, which is critical for resolving infections and inflammation, have prolonged CD8+ T-cell production of interferon-γ and TNF, and HLH-associated cytokine storm develops in such patients when they are infected with EBV or cytomegalovirus.64”
§ Cytokine Storm > Pathogen-Induced Cytokine Storm
What the sources say
- Not checked yetcites [64] Lykens JE, Terrell CE, Zoller EE, Risma K, Jordan MB. Perforin is a critical physiologic regulator of T-cell activation. Blood 2011; 118: 618- 626. 21606480 PMC3142903 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“recent studies in mice suggest that the cytokines and factors mediating the severity of cytokine storm are produced not by the CAR T cells but by macrophages and can be reversed by interleukin-6 and interleukin-1 blockade.52-54”
§ Cytokine Storm > Iatrogenic Cytokine Storm
What the sources say
- Not checked yetcites [52] Singh N, Hofmann TJ, Gershenson Z, et al. Monocyte lineage-derived IL-6 does not affect chimeric antigen receptor T-cell function. Cytotherapy 2017; 19: 867- 880. 28506444 PMC6676485 source
- Not checked yetcites [53] Giavridis T, van der Stegen SJC, Eyquem J, Hamieh M, Piersigilli A, Sadelain M. CAR T cell-induced cytokine release syndrome is mediated by macrophages and abated by IL-1 blockade. Nat Med 2018; 24: 731- 738. 29808005 PMC6410714 source
- Not checked yetcites [54] Norelli M, Camisa B, Barbiera G, et al. Monocyte-derived IL-1 and IL-6 are differentially required for cytokine-release syndrome and neurotoxicity due to CAR T cells. Nat Med 2018; 24: 739- 748. 29808007 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Since interleukin-6 blockade is highly effective at reversing symptoms and organ dysfunction in most patients, it is the likely cytokine driver of cytokine storm induced by CAR T-cell therapy.”
§ Cytokine Storm > Iatrogenic Cytokine Storm
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Patients with HHV-8–associated multicentric Castleman’s disease are immunocompromised as a result of human immunodeficiency virus infection or a genetic susceptibility, making it difficult to control the HHV-8 infection, which is a common, typically asymptomatic infection in the general population.69”
§ Cytokine Storm > Pathogen-Induced Cytokine Storm
What the sources say
- Not checked yetcites [69] Dispenzieri A, Fajgenbaum DC. Overview of Castleman disease. Blood 2020; 135: 1353- 1364. 32106302 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Though data on relative frequencies are limited, infections are most likely the most common trigger of cytokine storm.”
§ Cytokine Storm > Pathogen-Induced Cytokine Storm
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, the pathogen initiates and T-cell activation propagates cytokine storm in patients with a genetic susceptibility.”
§ Cytokine Storm > Pathogen-Induced Cytokine Storm
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A recent study showed that the effect of tocilizumab in patients with HHV-8–associated multicentric Castleman’s disease was minimal and short-lived, most likely because of viral interleukin-6 signaling that was independent of the neutralized interleukin-6 receptor.70”
§ Cytokine Storm > Pathogen-Induced Cytokine Storm
What the sources say
- Not checked yetcites [70] Ramaswami R, Lurain K, Peer CJ, et al. Tocilizumab in patients with symptomatic Kaposi sarcoma herpesvirus-associated multicentric Castleman disease. Blood 2020; 135: 2316- 2319. 32276276 PMC7316216 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Generalized T-cell and B-cell ablation with alemtuzumab and T-cell ablation with antithymocyte globulin have been reported; ablation most likely works by depleting the pathogenic CD8+ T cells, among other cell types.76”
§ Cytokine Storm > Monogenic or Autoimmune Cytokine Storm
What the sources say
- Not checked yetcites [76] Marsh RA, Allen CE, McClain KL, et al. Salvage therapy of refractory hemophagocytic lymphohistiocytosis with alemtuzumab. Pediatr Blood Cancer 2013; 60: 101- 109. 22522603 PMC3410971 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In patients with secondary HLH, viral, autoimmune, or neoplastic disorders trigger cytokine storm, and such patients often have heterozygous polymorphisms in the same genes that are altered in primary HLH.65,74”
§ Cytokine Storm > Monogenic or Autoimmune Cytokine Storm
What the sources say
- Not checked yetcites [65] Zhang M, Bracaglia C, Prencipe G, et al. A heterozygous RAB27A mutation associated with delayed cytolytic granule polarization and hemophagocytic lymphohistiocytosis. J Immunol 2016; 196: 2492- 2503. 26880764 PMC4779709 source
- Not checked yetcites [74] Kaufman KM, Linghu B, Szustakowski JD, et al. Whole-exome sequencing reveals overlap between macrophage activation syndrome in systemic juvenile idiopathic arthritis and familial hemophagocytic lymphohistiocytosis. Arthritis Rheumatol 2014; 66: 3486- 3495. 25047945 PMC4321811 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Cytokine storm was also reported in patients with SARS and was associated with poor outcomes.86”
§ Cytokine Storm > Covid-19–Associated Cytokine Storm
What the sources say
- Not checked yetcites [86] Huang K-J, Su I-J, Theron M, et al. An interferon-gamma-related cytokine storm in SARS patients. J Med Virol 2005; 75: 185- 194. 15602737 PMC7166886 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Given the primary genetic defects and the effective treatments that are available, innate cells are most likely the primary cell drivers involved, and TNF, interleukin-1, interleukin-18, or a combination of these cytokines probably drives pathogenesis.”
§ Cytokine Storm > Monogenic or Autoimmune Cytokine Storm
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“a recent randomized, controlled trial showing that dexamethasone reduces mortality among the most severe cases of Covid-19, characterized by elevated CRP levels and supplemental oxygen requirements, and potentially worsens outcomes in milder cases suggests that excessive, late-stage inflammation contributes to mortality.88”
§ Cytokine Storm > Covid-19–Associated Cytokine Storm
What the sources say
- Not checked yetcites [88] The RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19 — preliminary report. N Engl J Med. DOI: 10.1056/NEJMoa2021436. 32678530 PMC7383595 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Host immune responses and immune-related symptoms are extremely variable between asymptomatic patients (who have effective control of SARS-CoV-2) and patients with severe Covid-19 (who are unable to control the virus), which suggests that host immune dysregulation contributes to pathogenesis in some cases.”
§ Cytokine Storm > Covid-19–Associated Cytokine Storm
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“blocking a cytokine with a low or normal circulating level can be effective if it is a key component of the hyperinflammatory circuit or if its level is potentially elevated in tissue.”
§ Cytokine Storm > Therapeutics
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“combination therapy has more potential risks than single-agent therapy.”
§ Cytokine Storm > Therapeutics
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“An observational study suggesting that patients with Covid-19 have a good response to glucocorticoids when the CRP level is high but a poor response when the level is low is consistent with these findings.101”
§ Cytokine Storm > Covid-19–Associated Cytokine Storm
What the sources say
- Not checked yetcites [101] Keller MJ, Kitsis EA, Arora S, et al. Effect of systemic glucocorticoids on mortality or mechanical ventilation in patients with COVID-19. J Hosp Med 2020; 15: 489- 493. 32804611 PMC7518134 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“All targeted agents have target-specific risks”
§ Cytokine Storm > Therapeutics
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Likewise, the observation that proinflammatory agents such as inhaled interferon-β have a positive effect if given early in the disease course is consistent with a model in which immunostimulation that enhances antiviral activity is helpful early (and probably harmful late), whereas immunosuppression is helpful late and harmful early.”
§ Cytokine Storm > Covid-19–Associated Cytokine Storm
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The immune response to SARS-CoV-2 is critical for controlling viral replication and clearance.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“pathologic hyperinflammation itself is an immunodeficiency that can put patients at risk for infections”
§ Cytokine Storm > Therapeutics
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Targeted therapeutic approaches to cytokine storm associated with idiopathic multicentric Castleman’s disease, HLH, or CAR T-cell therapy have turned deadly conditions into often reversible states.”
§ Cytokine Storm > Summary
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
The paper relies on this without support.
The immune system is expected to recognize foreign invaders, respond proportionally to the pathogen burden, and then return to homeostasis.
“The immune system is expected to recognize foreign invaders, respond proportionally to the pathogen burden, and then return to homeostasis.”
The paper relies on this without support.
Cytokines have short half-lives, which normally prevents them from having effects outside lymphoid tissue and sites of inflammation.
“Cytokines have short half-lives, which normally prevents them from having effects outside lymphoid tissue and sites of inflammation.”
The paper relies on this without support.
The immune response to SARS-CoV-2 is critical for controlling viral replication and clearance.
“when the immune response to SARS-CoV-2 is critical in controlling viral replication and clearance.”
The paper relies on this without support.
No unifying definition of cytokine storm exists.
“No unifying definition of cytokine storm exists”
The paper relies on this without support.
There is much disagreement about what the definition of cytokine storm should be and whether specific conditions such as Covid-19 should be included in the spectrum of cytokine storm disorders.
“there is much disagreement about what the definition should be and whether specific conditions such as Covid-19 should be included in the spectrum of cytokine storm disorders.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“This specific activity protects severely infected COVID-19 patients from the cytokine storm (55).”
From DrugCentral 2023 extends human clinical data and integrates veterinary drugs (2023) · cites this paper as [55]
Citations
Cites
Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China
Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., Zhang, L., Fan, G., Xu, J., Gu, X., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30183-5 · Cited by 48,884
Dexamethasone in Hospitalized Patients with Covid-19
The RECOVERY Collaborative Group (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2021436 · Cited by 11,477
Effect of Dexamethasone in Hospitalized Patients with COVID-19 – Preliminary Report
Horby, P., Lim, W. S., Emberson, J., Mafham, M., Bell, J., Linsell, L., Staplin, N., Brightling, C., Ustianowski, A., Elmahi, E., et al. (2020) · doi:10.1101/2020.06.22.20137273 · Cited by 11,475
Mosmann, T. R., & Coffman, R. L. (1989) · Annual Review of Immunology · doi:10.1146/annurev.iy.07.040189.001045 · Cited by 7,692
Gout-associated uric acid crystals activate the NALP3 inflammasome
Martinon, F., Pétrilli, V., Mayor, A., Tardivel, A., & Tschopp, J. (2006) · Nature · doi:10.1038/nature04516 · Cited by 5,326
Korn, T., Bettelli, E., Oukka, M., & Kuchroo, V. K. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132710 · Cited by 4,873
Lee, D. W., Santomasso, B. D., Locke, F. L., Ghobadi, A., Turtle, C. J., Brudno, J. N., Maus, M. V., Park, J. H., Mead, E., Pavletic, S., et al. (2019) · Biology of Blood and Marrow Transplantation · doi:10.1016/j.bbmt.2018.12.758 · Cited by 3,675
Chimeric Antigen Receptor–Modified T Cells for Acute Lymphoid Leukemia
Grupp, S. A., Kalos, M., Barrett, D., Aplenc, R., Porter, D. L., Rheingold, S. R., Teachey, D. T., Chew, A., Hauck, B., Wright, J. F., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1215134 · Cited by 3,509
Self-citationCurrent concepts in the diagnosis and management of cytokine release syndrome.
Lee, D. W., Gardner, R., Porter, D. L., Louis, C. U., Ahmed, N., Jensen, M., Grupp, S. A., & Mackall, C. L. (2014) · Blood · doi:10.1182/blood-2014-05-552729 · Cited by 2,806
Autoantibodies against type I IFNs in patients with life-threatening COVID-19
Bastard, P., Rosen, L. B., Zhang, Q., Michailidis, E., Hoffmann, H.-H., Zhang, Y., Dorgham, K., Philippot, Q., Rosain, J., Béziat, V., et al. (2020) · Science · doi:10.1126/science.abd4585 · Cited by 2,662
Cited by
Sorted by citations
Interleukin-6 receptor antagonists in critically ill patients with Covid-19.
The REMAP-CAP Investigators (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2100433 · Cited by 1,962
Sun, L., Su, Y., Jiao, A., Wang, X., & Zhang, B. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01471-y · Cited by 1,153
Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19
Bonaventura, A., Vecchié, A., Dagna, L., Martinod, K., Dixon, D. L., Tassell, B. W. V., Dentali, F., Montecucco, F., Maßberg, S., Levi, M. M., et al. (2021) · Nature reviews. Immunology · doi:10.1038/s41577-021-00536-9 · Cited by 1,039
COVID-19 and the human innate immune system
Schultze, J. L., & Aschenbrenner, A. C. (2021) · Cell · doi:10.1016/j.cell.2021.02.029 · Cited by 714
“immune hyperactivation in cytokine storm is the failure of resolution of the inflammation (Fajgenbaum and June, 2020).”
BackgroundTherapeutic strategies for COVID-19: progress and lessons learned
Li, G., Hilgenfeld, R., Whitley, R. J., & Clercq, E. D. (2023) · Nature Reviews Drug Discovery · doi:10.1038/s41573-023-00672-y · Cited by 714
Metadata
- Authors
- Fajgenbaum, D. C., & June, C. H.
- Affiliations
- University of Pennsylvania (US)
- Parker Institute for Cancer Immunotherapy (US)
- Corresponding author
- June, Carl H.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2020-12-03
- Volume
- 383
- Issue
- 23
- Pages
- 2255-2273
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC7727315
- OpenAlex
- W3112902030
- Cited by
- 3,196
- References
- 113
- Citations by year
- 2026: 304 · 2025: 438 · 2024: 534 · 2023: 592 · 2022: 711 · 2021: 601 · 2020: 10
- FWCI
- 22.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (2r01hl141408-06)
- National Heart, Lung, and Blood Institute (R01-HL141408)
- National Cancer Institute (P01CA214278)
- Topics
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Sepsis Diagnosis and Treatment
- Keywords
- cytokine storm, pericarditis, heart disease, CTCAE grading, adverse event definitions
- MeSH terms
- Cytokine Release Syndrome, COVID-19, Autoimmune Diseases, Bacterial Infections, Blood Proteins, Humans, Interleukins, Virus Diseases, Cytokines, Chemokines
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
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