Cited by 794Sepsis Diagnosis and TreatmentInflammation biomarkers and pathwaysAntibiotics Pharmacokinetics and Efficacy

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Recombinant Human Interleukin 1 Receptor Antagonist in the Treatment of Patients With Sepsis Syndrome: Results From a Randomized, Double-blind, Placebo-Controlled Trial

Fisher, Charles J.·1994·JAMA

DOI 10.1001/jama.1994.03510470040032

Open this paper in CoChat — free account

Abstract

Objective. —To further define the safety and efficacy of recombinant human interleukin 1 receptor antagonist (rhIL-1ra) in the treatment of sepsis syndrome. Study Design. —Randomized, double-blind, placebo-controlled, multicenter, multinational clinical trial. Population. —A total of 893 patients with sepsis syndrome received an intravenous loading dose of rhIL-1ra, 100 mg, or placebo followed by a continuous 72-hour intravenous infusion of rhIL-1ra (1.0 or 2.0 mg/kg per hour) or placebo. Outcome Measure. —Twenty-eight—day all-cause mortality. Results. —There was not a significant increase in survival time for rhIL-1ra treatment compared with placebo among all patients who received the study medication (n=893; generalized Wilcoxon statistic,P=.22) or among patients with shock at study entry (n=713; generalized Wilcoxon statistic,P=.23), the two primary efficacy analyses specified a priori for this trial. Results from secondary analyses suggest an increase in survival time with rhIL-1ra treatment among patients with dysfunction of one or more organs (n=563; linear dose-response,P=.009). Retrospective analysis demonstrated an increase in survival time with rhIL-1ra treatment among patients with a predicted risk of mortality of 24% or greater (n=580; linear dose-response,P=.005) as well as among patients with both dysfunction of one or more organs and a predicted risk of mortality of 24% or greater (n=411; linear dose-response,P=.002). Conclusions. —There was not a statistically significant increase in survivial time for rhIL-1ra treatment compared with placebo among all patients who received the study medication or among patients with shock at study entry. Secondary and retrospective analyses of efficacy suggest that treatment with rhIL-1ra results in a dose-related increase in survival time among patients with sepsis who have organ dysfunction and/or a predicted risk of mortality of 24% or greater. (JAMA. 1994;271:1836-1843)

Integrity signals

Registry

Crossref · 10.1001/jama.1994.03510470040032

Cites

0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

The publisher hasn’t deposited this paper’s reference list.

Sorted by citations

Items 101–200 of 794

Prevalence of Hypophosphatemia in Sepsis and Infection: The Role of Cytokines
Barak, V., Schwartz, A., Kalickman, I., Nisman, B., Gurman, G., & Shoenfeld, Y. (1998) · The American Journal of Medicine · doi:10.1016/s0002-9343(97)00275-1 · Cited by 186
Apolipoprotein E Protects Against Bacterial Lipopolysaccharide-induced Lethality
Van Oosten, M., Rensen, P. C. N., Van Amersfoort, E. S., Van Eck, M., Van Dam, A.-M., Brevé, J. J. P., Vogel, T., Panet, A., Van Berkel, T. J. C., & Kuiper, J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m009915200 · Cited by 186
The efficacy and safety of plasma exchange in patients with sepsis and septic shock: a systematic review and meta-analysis
Rimmer, E. K., Houston, B. L., Kumar, A., Abou-Setta, A. M., Friesen, C., Marshall, J. C., Rock, G., Turgeon, A. F., Cook, D. J., Houston, D. S., et al. (2014) · Critical Care · doi:10.1186/s13054-014-0699-2 · Cited by 183
Changing pattern of organ dysfunction in early human sepsis is related to mortality
Russell, J. A., Singer, J., Bernard, G. R., Wheeler, A. P., Fulkerson, W., Hudson, L. D., Schein, R. M. H., Summer, W. R., Wright, P. E., & Walley, K. R. (2000) · Critical Care Medicine · doi:10.1097/00003246-200010000-00005 · Cited by 181
Acute lung injury and the acute respiratory distress syndrome
Luce, J. M. (1998) · Critical Care Medicine · doi:10.1097/00003246-199802000-00043 · Cited by 178
Multicenter, randomized, controlled trials evaluating mortality in intensive care: Doomed to fail?
Ospina-Tascón, G. A., Büchele, G. L., & Vincent, J. (2008) · Critical Care Medicine · doi:10.1097/ccm.0b013e318168ea3e · Cited by 174
Cytokines as Mediators in the Pathogenesis of Septic Shock
Dinarello, C. A. (1996) · Current topics in microbiology and immunology · doi:10.1007/978-3-642-80186-0_7 · Cited by 175
Eritoran tetrasodium (E5564) treatment for sepsis: review of preclinical and clinical studies
Barochia, A., Solomon, S., Cui, X., Natanson, C., & Eichacker, P. Q. (2011) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2011.558190 · Cited by 169
Macrophage Activation Syndrome and Secondary Hemophagocytic Lymphohistiocytosis in Childhood Inflammatory Disorders: Diagnosis and Management
Henderson, L. A., & Cron, R. Q. (2019) · Pediatric Drugs · doi:10.1007/s40272-019-00367-1 · Cited by 168
Inhibition of the NLRP3/IL‐1β axis protects against sepsis‐induced cardiomyopathy
Büsch, K., Kny, M., Huang, N. R., Klassert, T. E., Stock, M., Hahn, A., Graeger, S., Todiraş, M., Schmidt, S., Chamling, B., et al. (2021) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12763 · Cited by 178
Article Commentary: Sepsis, Systemic Inflammatory Response, and Multiple Organ Dysfunction: The Mystery Continues
Fry, D. E. (2012) · The American Surgeon · doi:10.1177/000313481207800102 · Cited by 204
Selective iNOS inhibition for the treatment of sepsis-induced acute kidney injury
Heemskerk, S., Masereeuw, R., Rüssel, F. G. M., & Pickkers, P. (2009) · Nature Reviews Nephrology · doi:10.1038/nrneph.2009.155 · Cited by 162
Acute Infectious Purpura Fulminans: Pathogenesis and Medical Management
Darmstadt, G. L. (1998) · Pediatric Dermatology · doi:10.1046/j.1525-1470.1998.1998015169.x · Cited by 156
ACUTE LUNG INJURY AND ACUTE RESPIRATORY DISTRESS SYNDROME IN SEPSIS AND SEPTIC SHOCK
Fein, A. M., & Calalang-Colucci, M. G. (2000) · Critical Care Clinics · doi:10.1016/s0749-0704(05)70111-1 · Cited by 158
Therapeutic Intervention and Targets for Sepsis
Rice, T. W., & Bernard, G. R. (2004) · Annual Review of Medicine · doi:10.1146/annurev.med.56.082103.104356 · Cited by 159
Cell-based Therapy for Acute Organ Injury
Monsel, A., Zhu, Y., Gennai, S., Hao, Q., Liu, J., & Lee, J. W. (2014) · Anesthesiology · doi:10.1097/aln.0000000000000446 · Cited by 158
PATHOGENESIS AND MANAGEMENT OF MULTIPLE ORGAN DYSFUNCTION OR FAILURE IN SEVERE SEPSIS AND SEPTIC SHOCK
BALK, R. A. (2000) · Critical Care Clinics · doi:10.1016/s0749-0704(05)70113-5 · Cited by 152
The 2022 EULAR/ACR points to consider at the early stages of diagnosis and management of suspected haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS)
Shakoory, B., Geerlinks, A. V., Wilejto, M., Kernan, K. F., Hines, M., Romano, M., Piskin, D., Ravelli, A., Sinha, R. R., Aletaha, D., et al. (2023) · Annals of the Rheumatic Diseases · doi:10.1136/ard-2023-224123 · Cited by 162
Hemorrhagic Shock Activation of NLRP3 Inflammasome in Lung Endothelial Cells
Xiang, M., Shi, X., Li, Y., Xu, J., Yin, L., Xiao, G., Scott, M. J., Billiar, T. R., Wilson, M. A., & Fan, J. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1102093 · Cited by 155
Monogenic autoinflammatory disorders: Conceptual overview, phenotype, and clinical approach
Nigrovic, P. A., Lee, P. Y., & Hoffman, H. M. (2020) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2020.08.017 · Cited by 162
Confirmatory platelet-activating factor receptor antagonist trial in patients with severe Gram-negative bacterial sepsis
Dhainaut, J.-F., Tenaillon, A., Hemmer, M., Damas, P., Tulzo, Y. L., Radermacher, P., Schaller, M., Sollet, J.-P., Wolff, M., Holzapfel, L., et al. (1998) · Critical Care Medicine · doi:10.1097/00003246-199812000-00021 · Cited by 152
Hemin inhibits NLRP3 inflammasome activation in sepsis-induced acute lung injury, involving heme oxygenase-1
Luo, Y., Jiang, L., Kang, K., Fei, D., Meng, X., Nan, C., Pan, S., Zhao, M., & Zhao, M. (2014) · International Immunopharmacology · doi:10.1016/j.intimp.2014.02.017 · Cited by 151
“Inhibition of the IL-1 pathway improved ALI scores in animal models [23], but most ARDS patients did not get much benefit from IL-1 receptor antagonist treatment [24].”
Background
Which Multicenter Randomized Controlled Trials in Critical Care Medicine Have Shown Reduced Mortality? A Systematic Review
Santacruz, C. A., Pereira, A. J., Celis, É., & Vincent, J. (2019) · Critical Care Medicine · doi:10.1097/ccm.0000000000004000 · Cited by 155
Immunotherapy in sepsis - brake or accelerate?
Steinhagen, F., Schmidt, S. V., Schewe, J., Peukert, K., Klinman, D. M., & Bode, C. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107476 · Cited by 152
SEVERE SEPSIS AND SEPTIC SHOCK: The Role of Gram-Negative Bacteremia
Munford, R. S. (2006) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev.pathol.1.110304.100200 · Cited by 150
Immature anti-inflammatory response in neonates
SCHULTZ, C., Temming, P., Bucsky, P., Göpel, W., Strunk, T., & Härtel, C. (2003) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2004.02313.x · Cited by 146
Recent advances in the pathophysiology and molecular basis of sepsis-associated organ dysfunction: Novel therapeutic implications and challenges
Hattori, Y., Hattori, K., Suzuki, T., & Matsuda, N. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.02.040 · Cited by 145
“However, such cytokinetargeted therapies for septic patients who may have dysfunction of one or more organs have not proven to be of clinical benefit in trials (Abraham et al., 1998, 2001; Fisher et al., 1994; Zeni et al., 1997).”
Anti-inflammatory therapies in sepsis and septic shock
Freeman, B. D., & Natanson, C. (2000) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.9.7.1651 · Cited by 146
The sirens' songs of confirmatory sepsis trials
Natanson, C., Esposito, C., & Banks, S. M. (1998) · Critical Care Medicine · doi:10.1097/00003246-199812000-00001 · Cited by 146
Economic Aspects of Severe Sepsis
Burchardi, H., & Schneider, H. (2004) · PharmacoEconomics · doi:10.2165/00019053-200422120-00003 · Cited by 144
Glucan-Based Macrophage Stimulators
Williams, D. L., Mueller, A., & Browder, W. (1996) · BioDrugs · doi:10.1007/bf03259335 · Cited by 145
Surfactant Therapy for Acute Lung Injury and Acute Respiratory Distress Syndrome
Raghavendran, K., Willson, D. F., & Notter, R. H. (2011) · Critical Care Clinics · doi:10.1016/j.ccc.2011.04.005 · Cited by 138
Cytokines and Adhesion Molecules in Elective and Accidental Trauma-Related Ischemia/Reperfusion
Seekamp, A., Jochum, M., Ziegler, M. G., van Griensven, M., Martin, M. U., & Regel, G. (1998) · doi:10.1097/00005373-199805000-00022 · Cited by 138
Interleukin-6 in the Cerebrospinal Fluid After Perinatal Asphyxia Is Related to Early and Late Neurological Manifestations
Martín‐Ancel, A., Garcı́a-Alix, A., Pascual‐Salcedo, D., et al. (1997) · PEDIATRICS · doi:10.1542/peds.100.5.789 · Cited by 139
HMGB-1 AS A THERAPEUTIC TARGET FOR INFECTIOUS AND INFLAMMATORY DISORDERS
Mantell, L. L., Parrish, W. R., & Ulloa, L. (2005) · Shock · doi:10.1097/01.shk.0000188710.04777.9e · Cited by 140
Acute respiratory distress syndrome heterogeneity and the septic ARDS subgroup
Xu, H., Sheng, S., Luo, W., Xu, X.-F., & Zhang, Z. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1277161 · Cited by 157
Increased Resistance Against Acute Polymicrobial Sepsis in Mice Challenged with Immunostimulatory CpG Oligodeoxynucleotides Is Related to an Enhanced Innate Effector Cell Response
Weighardt, H., Feterowski, C., Veit, M., Rump, M., Wagner, H., & Holzmann, B. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.8.4537 · Cited by 137
Anti-IL-10 Therapeutic Strategy Using the Immunomodulator AS101 in Protecting Mice from Sepsis-Induced Death: Dependence on Timing of Immunomodulating Intervention
Kalechman, Y., Gafter, U., Gal, R., et al. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.1.384 · Cited by 136
Introducing Critical Appraisal to studies of animal models investigating novel therapies in sepsis
Piper, R. D., Cook, D. J., Bone, R. C., & Sibbald, W. J. (1996) · Critical Care Medicine · doi:10.1097/00003246-199612000-00021 · Cited by 132
Plasma proinflammatory cytokine concentrations, Acute Physiology and Chronic Health Evaluation (APACHE) III scores and survival in patients in an intensive care unit
Friedland, J. S., Porter, J. C., Daryanani, S., Bland, J. M., Screaton, N. J., Vesely, M. J. J., Griffin, G. E., Bennett, E., & Remick, D. G. (1996) · Critical Care Medicine · doi:10.1097/00003246-199611000-00003 · Cited by 129
Relationship Between Plasma Cytokine Concentration and Multiple Organ Failure in Patients with Acute Pancreatitis
Hirota, M., Nozawa, F., Okabe, A., et al. (2000) · Pancreas · doi:10.1097/00006676-200008000-00006 · Cited by 124
The flavonoid baicalin inhibits superantigen‐induced inflammatory cytokines and chemokines
Krakauer, T., Li, B. Q., & Young, H. A. (2001) · FEBS Letters · doi:10.1016/s0014-5793(01)02584-4 · Cited by 124
Mitochondrial Peptides Are Potent Immune Activators That Activate Human Neutrophils Via FPR-1
Raoof, M., Zhang, Q., Itagaki, K., & Hauser, C. J. (2010) · The Journal of Trauma: Injury, Infection, and Critical Care · doi:10.1097/ta.0b013e3181dcd28d · Cited by 124
Interleukin-1 Receptor Antagonist Penetrates Human Brain at Experimentally Therapeutic Concentrations
Clark, S., McMahon, C. J., Gueorguieva, I., Rowland, M., Scarth, S., Georgiou, R. F., Tyrrell, P. J., Hopkins, S. J., & Rothwell, N. J. (2007) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600537 · Cited by 123
“This clinical condition may be associated with SAH, although relatively uncommon, and evidence from a large trial of IL-1RA in sepsis suggests that IL-1RA was not implicated in the development of cardiac problems in that patient cohort (Fisher et al, 1994).”
BackgroundMethodResultInfluential
The gasdermin family: emerging therapeutic targets in diseases
Zhu, C., Xu, S., Jiang, R., Yu, Y., Bian, J., & Zou, Z. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01801-8 · Cited by 149
Protection from experimental ventilator-induced acute lung injury by IL-1 receptor blockade
Frank, J. A., Pittet, J., Wray, C. M., & Matthay, M. A. (2007) · Thorax · doi:10.1136/thx.2007.079608 · Cited by 120
“[41] There was no overall mortality benefit for patients receiving IL-1Ra in the entire group; however, in the subgroup of 223 patients with ARDS and sepsis, there was a significant reduction in mortality in the those who received IL-1Ra (34% in patients receiving the 2 mg/h dose compared with 49% in the placebo group…”
BackgroundResult
Bacterial translocation in multiple organ failure: Cause or epiphenomenon still unproven
Lemaire, L. C. J. M., van Lanschot, J. J. B., Stoutenbeek, C. P., van Deventer, S. J. H., Wells, C. L., & Gouma, D. J. (1997) · British journal of surgery · doi:10.1111/j.1365-2168.1997.00520.x · Cited by 127
EFFECTS OF HIGH-DOSE OF INTRAVENOUS IMMUNOGLOBULIN AND ANTIBIOTICS ON SURVIVAL FOR SEVERE SEPSIS UNDERGOING SURGERY
Rodr??guez, A., Rello, J., Neira, J., Maskin, B. C., Ceraso, D., Vasta, L., & Pálizas, F. (2005) · Shock · doi:10.1097/01.shk.0000157302.69125.f8 · Cited by 125
Distinct downstream pathways of caspase-11 in regulating apoptosis and cytokine maturation during septic shock response
Kang, S. J., Wang, S., Kuida, K., & Yuan, J. (2002) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401087 · Cited by 117
Sepsis and Nosocomial Infection: Patient Characteristics, Mechanisms, and Modulation
Denstaedt, S. J., Singer, B. H., & Standiford, T. J. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02446 · Cited by 120
Targeting the host response in sepsis: current approaches and future evidence
Bode, C., Weis, S., Sauer, A., Wendel‐Garcia, P. D., & David, S. (2023) · Critical Care · doi:10.1186/s13054-023-04762-6 · Cited by 127
Targeted adenovirus-induced expression of IL-10 decreases thymic apoptosis and improves survival in murine sepsis
Oberholzer, C., Oberholzer, A., Bahjat, F. R., Minter, R. M., Tannahill, C. L., Abouhamze, A. S., LaFace, D., Hutchins, B., Clare-Salzler, M. J., & Moldawer, L. L. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.181338198 · Cited by 114
Heat stress increases survival rates in lipopolysaccharide-stimulated rats
Chu, E., Ribeiro, S. P., & Slutsky, A. S. (1997) · Critical Care Medicine · doi:10.1097/00003246-199710000-00025 · Cited by 111
The Metabolic Basis of Immune Dysfunction Following Sepsis and Trauma
McBride, M. A., Owen, A. M., Stothers, C. L., Hernandez, A., Luan, L., Burelbach, K. R., Patil, T. K., Bohannon, J. K., Sherwood, E. R., & Patil, N. K. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01043 · Cited by 120
Role of Mitochondrial Oxidative Stress in Sepsis
Nagar, H., Piao, S., & Kim, C. (2018) · Acute and Critical Care · doi:10.4266/acc.2018.00157 · Cited by 114
The Acute-on-Chronic Liver Failure Syndrome, or When the Innate Immune System Goes Astray
Clària, J., Arroyo, V., & Moreau, R. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1600818 · Cited by 112
“This finding opens new avenues for exploring anti-inflammatory therapies based on recombinant human IL-1ra, which has been shown to be effective in critically ill pediatric patients and in patients with sepsis and organ dysfunction and/or a predicted risk of mortality of $24% (39, 40).”
Background
Immunomodulatory effects of glycine on LPS‐treated monocytes: reduced TNF‐α production and accelerated IL‐10 expression
Spittler, A., Reissner, C. M., Oehler, R., Gornikiewicz, A., Gruenberger, T., Manhart, N., Brodowicz, T., Mittlboeck, M., Boltz‐Nitulescu, G., & Roth, E. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.3.563 · Cited by 112
Use of Predicted Risk of Mortality to evaluate the efficacy of anticytokine therapy in sepsis
Knaus, W. A., Harrell, F. E., LaBrecque, J. F., Wagner, D. P., Pribble, J. P., Draper, E. A., Fisher, C. J., & Soll, L. (1996) · Critical Care Medicine · doi:10.1097/00003246-199601000-00010 · Cited by 111
Self-citation
Exudate Macrophages Attenuate Lung Injury by the Release of IL-1 Receptor Antagonist in Gram-negative Pneumonia
Herold, S., Tabar, T. S., Janßen, H., Högner, K., Cabanski, M., Lewe-Schlosser, P., Albrecht, J., Driever, F., Vadász, I., Seeger, W., et al. (2011) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201009-1431oc · Cited by 117
Serious Infections Associated with Anticytokine Therapies in the Rheumatic Diseases
Giles, J. T., & Bathon, J. M. (2004) · Journal of Intensive Care Medicine · doi:10.1177/0885066604267854 · Cited by 110
Myocardial dysfunction in septic shock: Part II. Role of cytokines and nitric oxide
Kumar, A., Krieger, A. C., Symeoneides, S., Kumar, A., & Parrillo, J. E. (2001) · Journal of Cardiothoracic and Vascular Anesthesia · doi:10.1053/jcan.2001.25003 · Cited by 110
N-acetyl-L-cysteine depresses cardiac performance in patients with septic shock
Peake, S., Moran, J. L., & Leppard, P. (1996) · Critical Care Medicine · doi:10.1097/00003246-199608000-00006 · Cited by 107
Early immunoneutralization of calcitonin precursors attenuates the adverse physiologic response to sepsis in pigs
Wagner, K. E., Martinez, J. M., Vath, S. D., et al. (2002) · Critical Care Medicine · doi:10.1097/00003246-200210000-00021 · Cited by 107
Requirement for interleukin-12 in the pathogenesis of warm hepatic ischemia/reperfusion injury in mice
Lentsch, A. B., Yoshidome, H., Kato, A., Warner, R. L., Cheadle, W. G., Ward, P. A., & Edwards, M. J. (1999) · Hepatology · doi:10.1002/hep.510300615 · Cited by 105
Blocking IL-1 to prevent respiratory failure in COVID-19
van de Veerdonk, F. L., & Netea, M. G. (2020) · Critical Care · doi:10.1186/s13054-020-03166-0 · Cited by 106
Soluble E-Selectin Levels in Sepsis and Critical Illness
Cummings, C., Sessler, C. N., Beall, L. D., et al. (1997) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.156.2.9509017 · Cited by 105
Cardiac Fibroblasts Contribute to Myocardial Dysfunction in Mice with Sepsis: The Role of NLRP3 Inflammasome Activation
Zhang, W., Xu, X., Kao, R. L. C., Mele, T. S., Kvietys, P. R., Martin, C. M., & Rui, T. (2014) · PLoS ONE · doi:10.1371/journal.pone.0107639 · Cited by 106
“Clinical trials using IL-1-based therapies have been disappointing with no clear or consistent benefit in sepsis demonstrated [6,7].”
Background
Baicalin Improves Survival in a Murine Model of Polymicrobial Sepsis via Suppressing Inflammatory Response and Lymphocyte Apoptosis
Zhu, J., Wang, J., Sheng, Y., Zou, Y., Bo, L., Wang, F., Lou, J., Fan, X., Bao, R., Wu, Y., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035523 · Cited by 105
Tumor necrosis factor-? regulates secretion of the adipocyte-derived cytokine, leptin
Finck, B. N., & Johnson, R. W. (2000) · Microscopy Research and Technique · doi:10.1002/1097-0029(20000801)50:3 · Cited by 48
Pharmacological Regulation of Neuropathic Pain Driven by Inflammatory Macrophages
Kiguchi, N., Kobayashi, D., Saika, F., Matsuzaki, S., & Kishioka, S. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18112296 · Cited by 106
Inhibition of c-Jun-N-terminal Kinase Increases Cardiac Peroxisome Proliferator-activated Receptor α Expression and Fatty Acid Oxidation and Prevents Lipopolysaccharide-induced Heart Dysfunction
Drosatos, K., Drosatos-Tampakaki, Z., Khan, R. S., Homma, S., Schulze, P. C., Zannis, V. I., & Goldberg, I. J. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.272146 · Cited by 107
Sepsis after major visceral surgery is associated with sustained and interferon-γ–resistant defects of monocyte cytokine production
Weighardt, H., Heidecke, C.-D., Emmanuilidis, K., Maier, S., Bartels, H., Siewert, J., & Holzmann, B. (2000) · Surgery · doi:10.1067/msy.2000.104118 · Cited by 103
The future of the IL-1 receptor antagonist anakinra: from rheumatoid arthritis to adult-onset Still's disease and systemic-onset juvenile idiopathic arthritis
Kalliolias, G. D., & Liossis, S. C. (2008) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.17.3.349 · Cited by 100
Biologic Control of Injury and Inflammation: Much More than Too Little or Too Late
Guirao, X., & Lowry, S. F. (1996) · World Journal of Surgery · doi:10.1007/s002689900069 · Cited by 102
Management of sepsis in neutropenic patients: 2014 updated guidelines from the Infectious Diseases Working Party of the German Society of Hematology and Medical Oncology (AGIHO)
Penack, O., Becker, C., Buchheidt, D., Christopeit, M., Kiehl, M. G., von Lilienfeld‐Toal, M., Hentrich, M., Reinwald, M., Salwender, H. J., Schalk, E., et al. (2014) · Annals of Hematology · doi:10.1007/s00277-014-2086-0 · Cited by 102
Anakinra in children and adults with Still’s disease
Vastert, S. J., Jamilloux, Y., Quartier, P., Ohlman, S., Koskinen, L. O., Kullenberg, T., Franck‐Larsson, K., Fautrel, B., & Benedetti, F. D. (2019) · Lara D. Veeken · doi:10.1093/rheumatology/kez350 · Cited by 102
The Toll-Like Receptor-3 Agonist Polyinosinic:Polycytidylic Acid Triggers Nigrostriatal Dopaminergic Degeneration
Deleidi, M., Hallett, P. J., Koprich, J. B., Chung, C. Y., & Ole Isacson, A. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.2400-10.2010 · Cited by 104
“Peripheral immune responses generate inflammatory mediators that alter BBB permeability, allowing viruses to enter the CNS (Wang et al., 2004).”
BackgroundMethodInfluential
The Choice of Anesthetic Maintenance Technique Influences the Antiinflammatory Cytokine Response to Abdominal Surgery
Gilliland, H. E., Armstrong, M. A., Carabine, U. A., & McMurray, T. J. (1997) · Anesthesia & Analgesia · doi:10.1097/00000539-199712000-00039 · Cited by 112
Efficacy and safety of LY315920Na/S-5920, a selective inhibitor of 14-kDa group IIA secretory phospholipase A2, in patients with suspected sepsis and organ failure
Abraham, E. H., Naum, C. C., Bandi, V., et al. (2003) · Critical Care Medicine · doi:10.1097/01.ccm.0000053648.42884.89 · Cited by 101
Microbiologic Findings and Correlations with Serum Tumor Necrosis Factor–α in Patients with Severe Sepsis and Septic Shock
Cohen, J., & Abraham, E. H. (1999) · The Journal of Infectious Diseases · doi:10.1086/314839 · Cited by 101
Mortality Benefit of Recombinant Human Interleukin-1 Receptor Antagonist for Sepsis Varies by Initial Interleukin-1 Receptor Antagonist Plasma Concentration*
Meyer, N. J., Reilly, J. P., Anderson, B. J., Palakshappa, J. A., Jones, T. K., Dunn, T. G., Shashaty, M. G. S., Feng, R., Christie, J. D., & Opal, S. M. (2017) · Critical Care Medicine · doi:10.1097/ccm.0000000000002749 · Cited by 102
Pharmacologic therapies for adults with acute lung injury and acute respiratory distress syndrome
Adhikari, N. K. J., Burns, K. E. A., Meade, M. O., & Ratnapalan, M. (2004) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd004477.pub2 · Cited by 99
Exogenous interleukin-10 fails to decrease the mortality or morbidity of sepsis
Remick, D. G., Garg, S. J., Newcomb, D. E., Wollenberg, G. K., Huie, T., & Bolgos, G. L. (1998) · Critical Care Medicine · doi:10.1097/00003246-199805000-00025 · Cited by 100
Adhesion Molecules in Inflammatory Diseases
Gonz??lez-Amaro, R., D??az-Gonz??lez, F., & S??nchez-Madrid, F. (1998) · Drugs · doi:10.2165/00003495-199856060-00003 · Cited by 98
Recombinant human soluble thrombomodulin decreases the plasma high-mobility group box-1 protein levels, whereas improving the acute liver injury and survival rates in experimental endotoxemia
Nagato, M., Okamoto, K., Abe, Y., Higure, A., & Yamaguchi, K. (2009) · Critical Care Medicine · doi:10.1097/ccm.0b013e3181a55184 · Cited by 98
The role of the intestine in the pathophysiology and management of severe acute pancreatitis
Flint, R. S., & Windsor, J. A. (2003) · HPB · doi:10.1080/13651820310001108 · Cited by 98
Septic acute kidney injury: molecular mechanisms and the importance of stratification and targeting therapy
Morrell, E. D., Kellum, J. A., Pastor‐Soler, N. M., & Hallows, K. R. (2014) · Critical Care · doi:10.1186/s13054-014-0501-5 · Cited by 97
Common genetic variation in the gene encoding interleukin-1-receptor antagonist (IL-1RA) is associated with altered circulating IL-1RA levels
Rafiq, S., Stevens, K., Hurst, A. J., Murray, A., Henley, W., Weedon, M. N., Bandinelli, S., Corsi, A. M., Guralnik, J. M., Ferruci, L., et al. (2007) · Genes & Immunity · doi:10.1038/sj.gene.6364393 · Cited by 92
Blocking Interleukin‐1 in Rheumatic Diseases
Goldbach‐Mansky, R. T. (2009) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.05159.x · Cited by 97
Strategies for blocking the systemic effects of cytokines in the sepsis syndrome
Christman, J. W., Holden, E. P., & Blackwell, T. S. (1995) · Critical Care Medicine · doi:10.1097/00003246-199505000-00027 · Cited by 96
Erlotinib protects against LPS-induced Endotoxicity because TLR4 needs EGFR to signal
De, S., Zhou, H., DeSantis, D., Croniger, C. M., Li, X., & Stark, G. R. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1511794112 · Cited by 96
Drug repurposing to improve treatment of rheumatic autoimmune inflammatory diseases
Kingsmore, K. M., Grammer, A. C., & Lipsky, P. E. (2019) · Nature Reviews Rheumatology · doi:10.1038/s41584-019-0337-0 · Cited by 97
Emerging pharmacological therapies for ARDS: COVID-19 and beyond
Horie, S., McNicholas, B., Rezoagli, E., Pham, T. O., Curley, G., McAuley, D. F., O’Kane, C. M., Nichol, A., dos Santos, C. C., Rocco, P. R. M., et al. (2020) · Intensive Care Medicine · doi:10.1007/s00134-020-06141-z · Cited by 100
Precision Immunotherapy to Improve Sepsis Outcomes
Giamarellos‐Bourboulis, E. J., Kotsaki, A., Kotsamidi, I., Efthymiou, A., Koutsoukou, V., Ehler, J., Paridou, A., Frantzeskaki, F. G., Müller, M. C. A., Pickkers, P., et al. (2025) · JAMA · doi:10.1001/jama.2025.24175 · Cited by 122
Prognostic value of a simple evolving disseminated intravascular coagulation score in patients with severe sepsis*
Kinasewitz, G. T., Zein, J., Lee, G. L., Nazir, S. A., & Taylor, F. B. (2005) · Critical Care Medicine · doi:10.1097/01.ccm.0000181296.53204.de · Cited by 91
Critical Role of Kupffer Cell-Derived IL-10 for Host Defense in Septic Peritonitis
Emmanuilidis, K., Weighardt, H., Maier, S., Gerauer, K. E., Fleischmann, T., Zheng, X. X., Hancock, W. W., Holzmann, B., & Heidecke, C.-D. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.7.3919 · Cited by 91
Management of sepsis in neutropenia: guidelines of the infectious diseases working party (AGIHO) of the German Society of Hematology and Oncology (DGHO)
Penack, O., Beinert, T., Buchheidt, D., Einsele, H., Hebart, H. F., Kiehl, M. G., Massenkeil, G., Schiel, X., Schleicher, J., Staber, P. B., et al. (2006) · Annals of Hematology · doi:10.1007/s00277-006-0096-2 · Cited by 91
Roles of IL-1 and TNF in the decreased ileal muscle contractility induced by lipopolysaccharide
Lodato, R. F., Khan, A., Zembowicz, M. J., Weisbrodt, N. W., Pressley, T. A., Li, Y.-F., Lodato, J. A., Zembowicz, A., & Moody, F. G. (1999) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1999.276.6.g1356 · Cited by 88
The Society for Immunotherapy of Cancer perspective on regulation of interleukin-6 signaling in COVID-19-related systemic inflammatory response
Arnaldez, F. I., O'Day, S. J., Drake, C. G., Fox, B. A., Fu, B., Urba, W. J., Montesarchio, V., Weber, J. S., Wei, H., Wigginton, J. M., et al. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-000930 · Cited by 92
Gene profiling in human blood leucocytes during recovery from septic shock
Payen, D. M., Lukaszewicz, A., Bélikova, I., Faivre, V., Gélin, C., Rußwurm, S., Launay, J., & Sévenet, N. (2008) · Intensive Care Medicine · doi:10.1007/s00134-008-1048-1 · Cited by 95

Authors: Fisher, C. J.
Corresponding author: Fisher, Charles J.
ORCID: Fisher, Charles J.
Venue: JAMA
Publisher: American Medical Association (AMA)
Published: 1994-06-15
Volume: 271
Issue: 23
Pages: 1836
ISSN: 0002-9955 (ISSN-L)
0098-7484
DOI: 10.1001/jama.1994.03510470040032
OpenAlex: W4322697531
Cited by: 790
References: 0
Citations by year: 2026: 11 · 2025: 23 · 2024: 18 · 2023: 28 · 2022: 15 · 2021: 18 · 2020: 32 · 2019: 23 · 2018: 24 · 2017: 22 · 2016: 19 · 2015: 18 · 2014: 30 · 2013: 20 · 2012: 22
FWCI: 37.99
Type: journal article
Language: en
Open access: closed
Locations: JAMA (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
Health Sciences › Medicine › Pharmacology (medical) › Antibiotics Pharmacokinetics and Efficacy
Keywords: sepsis, septic shock, survival, organ dysfunction, mortality risk, dose-response relationship, drug safety, cytokine inhibition

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.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Recombinant Human Interleukin 1 Receptor Antagonist in the Treatment of Patients With Sepsis Syndrome: Results From a Randomized, Double-blind, Placebo-Controlled Trial

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks