Cited by 2,448Sepsis Diagnosis and TreatmentInflammation biomarkers and pathwaysImmune Response and Inflammation

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Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia

Tracey, Kevin J., Fong, Yuman, Hesse, David G., Manogue, Kirk R., Lee, Annette T., Kuo, George C., Lowry, Stephen F., Cerami, Anthony·1987·Nature

DOI 10.1038/330662a0

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Abstract

Bacterial infection of the mammalian bloodstream can lead to overwhelming sepsis, a potentially fatal syndrome of irreversible cardiovascular collapse (shock) and critical organ failure. Cachectin, also known as tumour necrosis factor, is a macrophage-derived peptide hormone released in response to bacterial lipopolysaccharide, and it has been implicated as a principal mediator of endotoxic shock, although its function in bacterial sepsis is not known. Anaesthetized baboons were passively immunized against endogenous cachectin and subsequently infused with an LD100 dose of live Escherichia coli. Control animals (not immunized against cachectin) developed hypotension followed by lethal renal and pulmonary failure. Neutralizing monoclonal anti-cachectin antibody fragments (F(ab')2) administered to baboons only one hour before bacterial challenge protected against shock, but did not prevent critical organ failure. Complete protection against shock, vital organ dysfunction, persistent stress hormone release and death was conferred by administration of antibodies 2 h before bacterial infusion. These results indicate that cachectin is a mediator of fatal bacteraemic shock, and suggest that antibodies against cachectin offer a potential therapy of life-threatening infection.

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Kimura, A., Kitajima, M., Nishida, K., Serada, S., Fujimoto, M., Naka, T., Fujii‐Kuriyama, Y., Sakamato, S., Ito, T., Handa, H., et al. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20172024 · Cited by 58
“20172024 2198 proinflammatory cytokines can prevent the development of septic shock in animal models (Tracey et al., 1987; Riedemann et al., 2003), the neutralizing of TNF-α or IL-1β had no sufficient clinical effects in critically ill patients (Fisher et al.”
Background
STRUCTURE-FUNCTION RELATIONSHIPS OF BACTERIAL ENDOTOXINS
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Tumor necrosis factor-alpha induces activation of coagulation and fibrinolysis in baboons through an exclusive effect on the p55 receptor.
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Self-citation
Lipopolysaccharide activates nuclear factor κB in rat intestine: role of endogenous platelet‐activating factor and tumour necrosis factor
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“Another central mediator of endotoxin shock is TNF (Tracey et al., 1987) which is known to activate p50-p65 and p50-c-Rel in vitro (Beg et al., 1994).”
Background
A CAT reporter construct allows ultrasensitive estimation of TNF synthesis, and suggests that the TNF gene has been silenced in non-macrophage cell lines.
Beutler, B., & Brown, T. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115137 · Cited by 55
Tumour necrosis factor and bacterial sepsis
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Crucial Role of TNF Receptors 1 and 2 in the Control of Polymicrobial Sepsis
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“TNF inhibitors protect mice from sepsis induced by LPS or bacteria inoculation (14, 15).”
Background
Rupert waterhouse and carl friderichsen: adrenal apoplexy
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Preclinical Sepsis Models
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Nitro-oleic acid protects against endotoxin-induced endotoxemia and multiorgan injury in mice
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“Along this line, TNF- neutralization with a TNF- antibody or a TNF- -soluble receptor (TNFsRp55) protects against septic shock in baboons (43) and mice (6, 25).”
Background
Orientin Inhibits HMGB1-Induced Inflammatory Responses in HUVECs and in Murine Polymicrobial Sepsis
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“For instance, neutralizing antibodies against TNF [74] reduces lethality in an animal model of endotoxemic/bacteremic shock.”
Background
A Critical Role for Phosphatidylinositol (3,4,5)-Trisphosphate–Dependent Rac Exchanger 1 in Endothelial Junction Disruption and Vascular Hyperpermeability
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“animal models (3, 43, 71), demonstrating that TNF-a is a”
Method
Role for monokines in the metabolic effects of endotoxin. Interferon-gamma restores responsiveness of C3H/HeJ mice in vivo.
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Proinflammatory mediator activity, endogenous antagonists and the systemic inflammatory response in intra-abdominal sepsis
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Tolerance to Endotoxin Prevents Mortality in Infected Thermal Injury: Association with Attenuated Cytokine Responses
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Self-citation
Induction of Cytokine Synthesis by Flagella from Gram-Negative Bacteria May Be Dependent on the Activation or Differentiation State of Human Monocytes
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“Animal models have shown that host-derived inflammatory mediators such as TNFa promote the strong inflammatory response observed during Salmonella infection of the intestinal mucosa (2, 6, 38, 39 ).”
Background
Inhibition of cytokine‐induced nitric oxide production by transforming growth factor‐beta 1 in human smooth muscle cells.
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Protective effects of interleukin-6 in lipopolysaccharide (LPS)-induced experimental endotoxemia are linked to alteration in hepatic anti-oxidant enzymes and endogenous cytokines
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Identification of the Bioactive Constituent and Its Mechanisms of Action in Mediating the Anti-Inflammatory Effects of Black Cohosh and Related Cimicifuga species on Human Primary Blood Macrophages
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Authors: Tracey, K. J., Fong, Y., Hesse, D. G., Manogue, K. R., Lee, A. T., Kuo, G. C., Lowry, S. F., & Cerami, A.
Affiliations: Cornell University (US)
Rockefeller University (US)
ORCID: Tracey, Kevin J.
Fong, Yuman
Kuo, George C.
Cerami, Anthony
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 1987-12
Volume: 330
Issue: 6149
Pages: 662-664
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/330662a0
OpenAlex: W2038434279
Cited by: 2,448
References: 1
Citations by year: 2026: 10 · 2025: 13 · 2024: 19 · 2023: 17 · 2022: 13 · 2021: 24 · 2020: 24 · 2019: 32 · 2018: 31 · 2017: 24 · 2016: 40 · 2015: 33 · 2014: 44 · 2013: 43 · 2012: 46
FWCI: 95.90
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Sepsis Diagnosis and Treatment
Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords: TNF-α, septic shock, bacteremia, Escherichia coli, passive immunization, neutralizing monoclonal antibodies, F(ab')2 fragments, endotoxic shock, organ failure, renal failure, respiratory failure, stress hormones, baboons, sepsis treatment
MeSH terms: Animals, Antibodies, Monoclonal, Blood Pressure, Cardiac Output, Catecholamines, Glucagon, Immunization, Passive, Immunologic Techniques, Leukocyte Count, Papio, Shock, Septic, Tumor Necrosis Factor-alpha, Sepsis

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Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia

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