Studies on the biologic relationship of endotoxin and other toxic proteins. I. Comparison of the properties of snake venom and endotoxin.

1. Agkistrodon piscivorus venom and E. coli endotoxin were shown to be immunologically distinct, and to differ in certain biologic properties: effects on immune response, body temperature, and circulating leukocyte count, and capacity to prepare for and provoke the local and generalized Shwartzman reaction. 2. Neither a single prior injection of venom nor the existence of hyperimmunity to lethal doses of venom protected rabbits against the local and generalized Shwartzman reaction. 3. Serial intravenous injections of sublethal doses of venom produced enhanced susceptibility to venom rather than refractoriness. 4. Preparation for both the local and generalized Shwartzman reaction with endotoxin appeared to enhance susceptibility of rabbits to challenge with venom. 5. Tolerance to bacterial pyrogens established by repeated injections of endotoxin is paralleled by increased resistance to snake venom given at least 1 week later, in mice and rabbits. 6. Zymosan failed to enhance susceptibility of rabbits to venom, but thorotrast increased the number of late deaths from venom. 7. Exposure of venom to ferrous sulfate interferes with its toxicity.