Journal ArticleDOI
Treatment of Septic Shock with the Tumor Necrosis Factor Receptor:Fc Fusion Protein
Charles J. Fisher,Jan M. Agosti,Steven M. Opal,Stephen F. Lowry,Robert A. Balk,Jerald C. Sadoff,Edward Abraham,Roland M. H. Schein,Ernest Benjamin +8 more
TLDR
In patients with septic shock, treatment with the TNFR:Fc fusion protein does not reduce mortality, and higher doses appear to be associated with increased mortality.Abstract:
Background A recombinant, soluble fusion protein that is a dimer of an extracellular portion of the human tumor necrosis factor (TNF) receptor and the Fc portion of IgG1 (TNFR:Fc) binds and neutralizes TNF-α and prevents death in animal models of bacteremia and endotoxemia. Methods To evaluate the safety and efficacy of TNFR:Fc in the treatment of septic shock, we conducted a randomized, double-blind, placebo-controlled, multicenter trial. A total of 141 patients were randomly assigned to receive either placebo or a single intravenous infusion of one of three doses of TNFR:Fc (0.15, 0.45, or 1.5 mg per kilogram of body weight). The primary end point was mortality from all causes at 28 days. Results There were 10 deaths among the 33 patients in the placebo group (30 percent mortality), 9 deaths among the 30 patients receiving the low dose of TNFR:Fc (30 percent mortality), 14 deaths among the 29 receiving the middle dose (48 percent mortality), and 26 deaths among the 49 receiving the high dose (53 percent...read more
Citations
More filters
Journal ArticleDOI
The role and regulation of apoptosis in sepsis.
Doreen E. Wesche-Soldato,Joanne Lomas-Neira,Mario Perl,Leslie N Jones,Chun-Shiang Chung,Alfred Ayala +5 more
TL;DR: Inhibition of FasL—Fas signaling protects septic mice from the onset of marked apoptosis and the morbidity/mortality seen in sepsis, and this extrinsic apoptosis response appears to utilize aspects of the Bid-induced mitochondrial pathway.
Journal ArticleDOI
Kidney and Liver Injuries After Major Burns in Rats Are Prevented by Resolvin D2.
Yoshitaka Inoue,Yong Ming Yu,Yong Ming Yu,Tomohiro Kurihara,Tomohiro Kurihara,Aleksandr Vasilyev,Amir Ibrahim,Rahmi Oklu,Gaofeng Zhao,Gaofeng Zhao,Anil V. Nair,Dennis Brown,Alan J. Fischman,Alan J. Fischman,Ronald G. Tompkins,Daniel Irimia,Daniel Irimia,Daniel Irimia +17 more
TL;DR: Pathologic changes in kidney and liver tissues in a rat model of major burn and endotoxin insults are ameliorated by resolvin D2, and significant tissue damage in the kidneys and liver is found.
Journal ArticleDOI
Lipopolysaccharide desensitizes monocytes–macrophages to CD40 ligand stimulation
Anna Sinistro,Chiara Ciaprini,Silvia Natoli,Emanuele Sussarello,Francesca Ippolita Calò Carducci,Cristiana Almerighi,M. Capozzi,Francesca Bolacchi,G. Rocchi,Alberto Bergamini +9 more
TL;DR: It is proposed that in vitro CD40L tolerance may be an appropriate model of monocyte alteration observed during septic immunosuppression and may help in the development of novel therapeutic strategies.
Journal ArticleDOI
Differential changes in gene expression in human neutrophils following TNF‐α stimulation: Up‐regulation of anti‐apoptotic proteins and down‐regulation of proteins involved in death receptor signaling
Direkrit Chiewchengchol,Helen L. Wright,Huw B. Thomas,Connie Lam,Kate J. Roberts,Nattiya Hirankarn,Michael W. Beresford,Robert J. Moots,Steven W. Edwards +8 more
TL;DR: Data indicate that when neutrophils are triggered by TNF‐α exposure, they undergo molecular changes in transcriptional expression to up‐regulate expression of specific anti‐apoptotic proteins and concomitantly decrease expression of Specific proteins involved in death receptor signaling which will alter their function in T NF‐α rich environments.
References
More filters
Journal ArticleDOI
Members of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee: American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis
Roger C. Bone,Robert A. Balk,F. B. Cerra,R. P. Dellinger,A. M. Fein,William A. Knaus,Roland M. H. Schein,W. J. Sibbald,WA Knous,J. H. Abrams,G. R. Bernard,JW Biondi,JE Calvin,R Demling,PJ Fahey,CJ Fisher,C Franklin,KJ Gorelick,MA Kelley,DG Maki,JC Marshall,WW Merrill,JP Pribble,EC Rackow,Timothy C. Rodell,JN Sheagren,Michael R. Silver,C. L. Sprung,Richard C. Straube,MJ Tobin,GM Trenholme,DP Wagner,CD Webb,JC Wherry,HP Wiedemann,CH Wortel,M. Kylänpää-Bäck +36 more
Journal ArticleDOI
The APACHE III prognostic system. Risk prediction of hospital mortality for critically ill hospitalized adults.
William A. Knaus,Douglas P. Wagner,Elizabeth A. Draper,Jack E. Zimmerman,Marilyn Bergner,Paulo G. Bastos,Carl A. Sirio,Donaldj Murphy,Ted Lotring,Anne M. Damiano +9 more
TL;DR: The overall predictive accuracy of the first-day APACHE III equation was such that, within 24 h ofICU admission, 95 percent of ICU admissions could be given a risk estimate for hospital death that was within 3 percent of that actually observed.
Journal ArticleDOI
Shock and tissue injury induced by recombinant human cachectin.
Kevin J. Tracey,Bruce Beutler,Stephen F. Lowry,James P Merryweather,Stephen D. Wolpe,Ian W. Milsark,Robert J. Hariri,Thomas J. Fahey,Alejandro Zentella,J. D. Albert,G. Tom Shires,Anthony Cerami +11 more
TL;DR: It appears that a single protein mediator (cachectin) is capable of inducing many of the deleterious effects of endotoxin.
Journal ArticleDOI
Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia
Kevin J. Tracey,Kevin J. Tracey,Yuman Fong,David G. Hesse,Kirk R. Manogue,Annette T. Lee,George C. Kuo,Stephen F. Lowry,Anthony Cerami +8 more
TL;DR: Protection against shock, vital organ dysfunction, persistent stress hormone release and death was conferred by administration of antibodies 2 h before bacterial infusion, indicating that cachectin is a mediator of fatal bacteraemic shock and suggesting that antibodies against Cachectin offer a potential therapy of life-threatening infection.
Journal ArticleDOI
Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin
TL;DR: The data suggest that cachectin/TNF is one of the principal mediators of the lethal effect of endotoxin, and this effect was dose-dependent and was most effective when the antiserum was administered prior to the injection of the endotoxin.