Anti-Interleukin-1 Strategies in the Treatment of the Septic Shock Syndrome

The septic shock syndrome has recently been termed the systemic inflammatory response syndrome (SIRS). It is an acute illness characterized by generalized activation of the endothelium. The most severe and most common form of the syndrome is found in patients wilh shock due to Gram-negative sepsis. In this overview. both animal and limited human data are considered for the contribution of the cytokine interleukin-1 (IL-1) to this syndrome. Cytokines are small molecular weight, endogenously produced proteins with multiple biological effects. Laboratory investigations suggest that IL-1 plays a critical role in SIRS by promoting the biochemical and clinical characteristics of SIRS. The biochemical changes induced by IL-1 are similar to those of tumour necrosis factor (TNF) and include increased synthesis of nitric oxide, prostaglandins, platelet activating factor and endothelial cell adhesion molecules. Togelher, IL-1 and TNF appear to act in a synergistic fashion in a variety of disease models. particularly SRIS. Specific blockade of IL-1 using soluble IL-1 receptors or IL-1 receptor antagonist suggests that blocking this cytokine may be useful in treating human SIRS