PREVENTION OF THE LOCALIZED AND GENERALIZED SHWARTZMAN REACTIONS BY AN ANTICOMPLEMENTARY AGENT, COBRA VENOM FACTOR

Abstract

Both localized and generalized Shwartzman reactions were induced in the same rabbits by simultaneous administration of preparatory intravenous and intradermal doses of endotoxin followed in 24 hr by the provocative dose. Control rabbits with more than 80% positive responses showed corresponding changes of platelet, white blood cell, fibrinogen, and hemolytic complement levels. Circulating fibrinogen and fibrin degradation products were detected shortly after the preparatory dose and persisted for at least 3 days. Rabbits given cobra venom anticomplementary factor showed hypocomplementemia (less than 10% of normal), leukocytosis, and elevated fibrinogen levels. After the administration of endotoxin, only one of 15 CVF-treated animals developed a Shwartzman reaction and that was mild. These rabbits showed only minor changes of platelet and fibrinogen levels throughout the experiment although their white blood cell responses were similar to those of the control group. No detectable fibrinogen and fibrin degradation products appeared in circulation, and the hemolytic complement activity increased gradually beginning with the preparatory dose of endotoxin. Thus depletion of terminal complement components (mainly C3) in rabbits is protective against the development of both localized and generalized Shwartzman reactions; its mechanism of action is probably through the sparing of platelets by inhibiting platelet-endotoxin interaction. The essential role of the complement system in Shwartzman reaction indicates that this coagulopathy probably represents a manifestation of immunologic injury.