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June 15, 1994

Sepsis Therapy TrialsContinued Disappointment or Reason for Hope?

JAMA. 1994;271(23):1876-1878. doi:10.1001/jama.1994.03510470080040

Solid experimental and clinical data place interleukin 1 (IL-1) directly in the midst of the cascade of mediators leading to organ system dysfunction and death in sepsis. For example, infusion of IL-1 into animals produces hypotension and organ system dysfunction, a pattern similar to that seen clinically in severe infection.1 Increased circulating levels of IL-1 appear to signal a poor prognosis in patients with sepsis.2 In several animal models of endotoxemia or bacteremia, survival is improved when the actions of IL-1 are blocked by infusion of the naturally occurring IL-1 receptor antagonist (IL-1ra).3,4 Perhaps most important, an unblinded, placebo-controlled study of IL-1ra therapy in critically ill patients with sepsis demonstrated a reduction in 28-day all-cause mortality from 44% in the placebo group to 16% in patients receiving high-dose IL-1ra therapy.5

See also p 1836.

In this issue of THE JOURNAL, Fisher et al6 report the