[Therapeutic strategies against mediators of septic shock].

The growing knowledge on the pathophysiological role of cytokines in septic shock stimulated efforts to control their synthesis and action pharmacologically in clinical situations. Among the various compounds elaborated by monocytes/macrophages in response to endotoxins, tumor necrosis factor alpha (TNF) and interleukin-1 (IL-1) have been recognized to be of particular importance for endotoxic effects. Therefore, therapeutic strategies in septic shock may benefit from antagonism or inhibition of these mediators. Anti-TNF-antibodies as well as pentoxifylline, an inhibitor of TNF synthesis, attenuated lethality provoked by endotoxin or sepsis in experimental animals. Furthermore, application of IL-1 receptor antagonist was able to counteract endotoxicity in animals. Based on these promising findings, controlled clinical studies have been started to define the precise clinical efficacy of the a.m. therapeutic strategies.