The ability of soluble cytokine receptors to alter the inflammatory responses to intravenous endotoxin will be evaluated in normal volunteers (Protocol 92-CC-0141). In two separate Phase I/II trials, soluble IL-1 receptor and soluble TNF receptor will be given intravenously to normal humans. The first phase of each study (either IL-IR or TNFR) will evaluate the safety and pharmacokinetics of infused recombinant human IL-IR or TNFR. The second phase will evaluate the ability of these cytokine receptors to alter the inflammatory responses and changes in systemic hemodynamics that occur following intravenous endotoxin. These studies will evaluate the role of these anti- inflammatory agents in a human model of acute inflammation. Using selective inhibitors to potent proinflammatory cytokines, this study will provide information regarding early host responses to bacterial products and establish a scientific basis for these new therapies in human septic shock.
