Role of interleukin-1 and the therapeutic potential of interleukin-1 receptor antagonist in sepsis.
Clinical trials of anticytokines in sepsis have not been as straightforward as had been anticipated from results in animal models of sepsis and the role of cytokines in sepsis is now in question. Retrospective analysis of the results of a phase III trial of interleukin-1 (IL-1) receptor antagonist suggests that sepsis-induced adult respiratory distress syndrome (ARDS), disseminated intravascular coagulation (DIC), renal dysfunction, and shock are valuable markers of patients in whom IL-1 is a pathogenic mediator and in whom IL-1ra can reduce mortality. A re-examination of the effects of IL-1ra in animal models of sepsis supports the validity of this analysis. A new phase III clinical trial will confirm or disprove the hypothesis that IL-1 is a mediator of pathology, and IL-1ra is a valuable therapy for sepsis complicated by ARDS, DIC, renal dysfunction, or shock.
Fisher
C J
CJ
Department of Pulmonary and Critical Care Medicine, Cleveland Clinic Foundation, OH 44195, USA.
Opal
S M
SM
Lowry
S F
SF
Sadoff
J C
JC
LaBrecque
J F
JF
Donovan
H C
HC
Lookabaugh
J L
JL
Lemke
J
J
Pribble
J P
JP
Stromatt
S C
SC
D004211:Disseminated Intravascular Coagulation / Q000209:etiology; D004311:Double-Blind Method; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000502:physiology*; D007674:Kidney Diseases / Q000150:complications / Q000209:etiology; D010919:Placebos; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D012128:Respiratory Distress Syndrome / Q000209:etiology; D018805:Sepsis / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D012769:Shock / Q000209:etiology; D012795:Sialoglycoproteins / Q000494:pharmacology*; D015996:Survival Rate
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D010919:Placebos; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins