Studies on the biologic relationship of endotoxin and other toxic proteins. II. Enhancement of susceptibility to snake venom by endotoxin.

1. Injections of sublethal quantities of Agkistrodon piscivorus venom into endotoxin-treated rabbits produces a consistent early death. 2. The endotoxin-induced hypersusceptibility state (EIHS) to venom is produced by intravenous, intradermal, and intraperitoneal administration of endotoxin. The latency and duration of the EIHS vary with the route of administration. 3. EIHS is induced by as little as 1 gamma of endotoxin administered intravenously. Although the degree of susceptibility was no greater with a 100 gamma dose than with 1 gamma, 1 mg of endotoxin made the rabbits susceptible to smaller venom doses. 4. EIHS was demonstrated with intravenous, intradermal and intraperitoneal injection of Agkistrodon piscivorus venom. Endotoxin-pretreated animals were not as susceptible to venom given intramuscularly. 5. Normal rabbits are very resistant to venom given intradermally and intraperitoneally. 6. Enhanced susceptibility to intravenous endotoxin was demonstrated in animals pretreated with sublethal doses of moccasin venom. It differed from EIHS in its short duration and its outcome: a late, slowly progressive death. 7. EIHS was demonstrated with other venoms: Crotalus adamanteus and Vipera russellii, and in a modified form (resulting in late death) with Notechis scutatus. Endotoxin pretreatment had no effect on susceptibility to Naja flava, Bungarus candidus, or Crotalus durissus terrificus venoms. 8. Major hypotheses regarding the nature of endotoxin-induced alterations in non-specific resistance were considered in relation to EIHS to venom.