Interleukin-1 Receptor Antagonist Circulates in Experimental Inflammation and in Human Disease

lnterleukin-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