INCREASED SUSCEPTIBILITY TO ENDOTOXIN-SHOCK IN COMPLEMENT-C3-DEFICIENT AND COMPLEMENT-C4-DEFICIENT MICE IS CORRECTED BY C1-INHIBITOR REPLACEMENT

Endotoxin shock is a life-threatening syndrome associated with a Gram- negative infection and mediated by a systemic inflammatory response, A s a major effector of inflammation, the complement system has been imp licated in both the pathogenesis and the protection from endotoxin sho ck, To clarify the role of complement in endotoxin shock, we have used mice totally deficient in either complement component C3 or C4, We fo und that both the C3- and C4-deficient mice were significantly more se nsitive to endotoxin than wild-type controls, The endotoxin-challenged complement-deficient mice failed to clear endotoxin efficiently from the circulation and this led to excess consumption of C1 inhibitor pro tein (C1 INH), a major regulator of both complement and the contact sy stem of blood coagulation, Replacement of C1 INH rescued the endotoxin -challenged complement-deficient mice from shock and death, These find ings suggest a novel therapy for treatment of endotoxemia with C1 INH protein.