Elevation of IL-18 in human sepsis

Interleukin-18 (IL-18) is a recently identified immunoregulatory cytokine t hat shares biochemical features with IL-1 beta and acts in part by inducing interferon-gamma (IFN-gamma). Endotoxic bacterial lipopolysaccharide (LPS) (1 or 2 ng/kg) was insufficient to increase plasma IL-18 in five healthy a dults measured 3, 12, and 24 hr following challenge. In contrast, in the fi rst 96 hr of admission to the surgical intensive carl unit, mean maximal se rum IL-18 was elevated(1122 +/- 259 pg/ml) in nine septic patients compared to six healthy adults (191 +/- 42, pg/ml), P < 0.01). Serum IL-18 concentr ations in septic patients did not correlate with other measured inflammator y mediators: tumor necrosis factor, IL-6, IL-10, or secretory leukocyte pro tease inhibitor. Therefore, IL-18 circulates in healthy adults and is a com ponent of the human systemic inflammatory response. Further, stimuli other than LPS may induce IL-18 production in vivo in human sepsis.