Sepsis Therapy Trials

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.¹Increased circulating levels of IL-1 appear to signal a poor prognosis in patients with sepsis.²In 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).³,⁴Perhaps 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 ofTHE JOURNAL, Fisher et al⁶report the