INTERLEUKIN-1 MEDIATES INCREASED PLASMA-LEVELS OF EICOSANOIDS AND CYTOKINES IN PATIENTS WITH SEPSIS SYNDROME

The purpose of this was to study evaluate the effects of interleukin-1 (IL-1) inhibition by human recombinant IL-1 receptor antagonist (IL-1 ra) on plasma prostaglandin, leukotriene, and cytokine levels in sepsi s syndrome. As part of a multisite, prospective, randomized, double-bl ind, placebo-controlled clinical trial, 19 septic patients received IL -1ra in a 100 mg bolus followed by 2.0 mg/kg/h i.v. for 72 h (n = 10) or placebo (n = 9). Plasma thromboxane B-2 (TXB(2)), prostagandin 6-ke to-F1 alpha (PGI), leukotriene B-4 (LTB(4)), leukotrienes C(4)D(4)E(4) (LTC(4)D(4)E(4)), IL-1 beta, IL-6, and tumor necrosis factor alpha (T NF) were measured by ELISA before study drug infusion (baseline) and a t 24, 48, 72, and 96 h after the beginning of the study drug infusion. Differences between placebo and IL1-ra for plasma LTB(4) and TNF were not significant. Plasma TXB(2), PGI, LTC(4)D(4)E(4), and IL-6, expres sed as % baseline, were significantly lower in patients receiving IL-1 ra than in the placebo group (p <.05), while plasma IL-1 was increased significantly. IL-1 may be a necessary mediator of increased circulat ing PGI, TXB2, LTC(4)D(4)E(4), and IL-6 levels in patients with sepsis syndrome. Plasma IL-1 is increased with infusion of IL-1ra. The clini cal significance of IL-1 in modifying circulating eicosanoid and cytok ine concentrations in clinical sepsis is not clear from the data.