Interleukin-1 receptor antagonist circulates in experimental inflammation and in human disease

Abstract

Interleukin-1 receptor antagonist (IL-1ra) is a 22-Kd protein that shares homology with IL-1β, binds to the IL-1 receptor, but has no known agonist properties. This inhibitor appears to be the first cytokine whose sole function is to block the actions of another cytokine. Exogenous IL-1ra administration has been shown to reduce mortality in experimental septic shock. We now report that IL-1ra is endogenously produced and circulates in experimental inflammation and in clinical disease. After experimental endotoxemia in human volunteers, IL-1ra concentrations increase from a baseline concentration of 460 ± 200 pg mL-1 to 14,870 ± 290 pg mL-1 at 3 hours (P < .05). IL-1ra is also detectable in all plasma samples from critically ill patients with a mean concentration of 8,680 ± 2,060 pg mL-1 (range 320 to 55,370 pgs mL-1). In nonhuman primates, Escherichia coli septic shock induces elevated plasma levels of IL-1ra (P < .05). However, in animals that eventually succumb to septic shock, II-1ra appears in quantities presumed inadequate to block the pathologic sequelae associated with high IL-1β levels. The findings suggest that IL-1ra may play a role in modulating the systemic host responses to a variety of nonlethal disease states by altering the balance between cytokines and their antagonists. © 1992 by The American Society of Hematology.