STUDIES ON THE BIOLOGIC RELATIONSHIP OF ENDOTOXIN AND OTHER TOXIC PROTEINS

Abstract

Endotoxin-induced alterations in nonspecific resistance, known to increase susceptibility to bacteria and viruses, also affect the resistance of rabbits to some snake venoms: Agkistrodon piscivorus, Crotalus adamanteus, Notechis scutatus, and Vipera russellii, but not others: Naja flava, Crotalus durissus terrificus, Bungarus candidus. The model of the endotoxin-induced hypersuscepti-bility state (EIHS) to venom was defined using Agkistrodon piscivorus venom. EIHS may be induced by intradermal, intravenous, or intraperitoneal administration of Escherichia coli endotoxin. It is produced by as little as 1 gamma of endotoxin intravenously; 100 gamma induced susceptibility by all 3 routes, but latency and duration varied with the route. The latent period was 30-45 minutes when 100 gamma endotoxin was given intravenously, and the duration at least 7 days. EIHS is demonstrable with intradermal, intraperitoneal, intravenous, and intramuscular venom. Normal animals were highly resistant to venom given intradermally or intraperitoneally; endotoxin-treated rabbits showed greatly enhanced susceptibility to venom by these routes. The mechanism of EIHS to venom is unknown. It does not reflect merely the additive effect of the two toxins, since very different results were noted when venom was given before endotoxin. We believe EIHS to venom presents a model for study of nonspecific resistance and that several aspects of these venom studies bear on major hypotheses regarding the locus of endotoxin-induced changes in resistance: the reticuloendothelial system, properdin levels, blood-tissue barriers (blood-brain barrier in particular), hemodynamic mechanisms (shock), iron metabolism, and others. Analysis of the toxic activities of venoms that elicit EIHS versus those that do not elicit it offers a further approach.