Blocking IL-1 reduces systemic cytokine release. Animals received lipopolysaccharide (LPS) or treatment with IL-1Ra immediately before LPS exposure (RA). Plasma levels of IL-1β and IL-6 were measured by ELISA at 2, 6, and 24 hours. Pre-emptive administration of IL-1Ra significantly reduced the amount of plasma IL-1β at six hours (a * P < 0.01 vs LPS) and 24 hours (*** P < 0.001 vs LPS). IL-6 followed a similar trend, with a strong decrease in plasma concentrates at six hours (b *** P < 0.001 vs LPS) and at 24 hours (** P < 0.001 vs LPS). To corroborate the findings, levels of IL-1β and IL-6 were measured in IL-1R-/- (-/-) (a to b, *** P < 0.0001 and ** P < 0.001 vs LPS respectively). (c) IL-1Ra or IL-1R-/- had no effects on HMGB-1 release in plasma. Data are expressed as mean ± standard error of the mean (n = 6) and compared by one-way and two-way (IL1R-/-) analysis of variance and Student-Newman-Keuls method.