Role of Complement Activation in Human Sepsis and Septic Shock

The hemodynamic changes in septic shock in man have been thoroughly studied and are now well documented [1,2]. However, the pathogenetic mechanisms and intermediate events leading from uncomplicated bacteremia to the circulatory disturbance of septic shock are less well understood. Activation of the complement system has been implicated as one of the possible mechanisms, since it may be associated with peripheral vasodilation as observed in human septic shock [3]. Experimental studies in various animal species have yielded some conflicting results but the very early, transient and relatively benign hypotensive response to endotoxin injection can be related to complement activation [4]. The later prolonged and potentially fatal hypotension appears not to be related to complement activation [4]. In some animal models activation of the complement system has even a major protective effect against otherwise lethal doses of endotoxin. Therefore, the role of complement in mediating or, alternatively, protecting against experimental endotoxin shock remains unclear [4].