[Activation of plasma cascade systems in sepsis: role of C1 inhibitors]

During sepsis the complement system, the contact activation system and the coagulation cascade are activated. Activation of these plasmatic cascades contributes to the development of multiple organ failure and the high mortality rate of severe sepsis and septic shock. C1-inhibitor is the main inhibitor of the classical pathway of the complement system (C1s and C1r), of the contact activation system (factor XIIa and kallikrein) and of the intrinsic pathway of coagulation (factor XIa). During sepsis, C1-inhibitor is proteolytically inactivated. The increase of inactivated C1-inhibitor in plasma correlates positively with mortality in septic patients. C1-inhibitor substitution has been shown to reduce the mortality in experimental animals with severe sepsis or septic shock. Only a few cases of C1-inhibitor substitution in patients with severe sepsis or septic shock have been reported. C1-inhibitor has been shown to attenuate the activation of the complement system and the contact activation system and to improve hypotension. Based on this convincing pathophysiological concept and the results of the animal studies, we initiated the "Bernese C1-inhibitor study", a randomised double-blind and placebo-controlled pilot study involving administration of C1-inhibitor to patients with severe sepsis or septic shock. If the results of this pilot study confirm the results of the reports mentioned above, they will serve as a base for larger multicentre studies.