Relationship of Body Temperature to the Lethal Action of Bacterial Endotoxin*

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Abstract
Induction of fever in rabbits by physical means (elevation of environmental temperature) or by pharmacological means (administration of D-lysergic acid diethyl-amide, LSD) reduces LD50 of bacterial endotoxin from approximately 240 [mu]g/kg to 4-13 [mu]gAg. Hyperthermic rabbits exhibit augmented febrile responses to endotoxin and die more rapidly. Rabbits shorn of their fur become hypothermic in response to endotoxic challenge at room temperature. Also, the LD50 of endotoxin is approximately 10 times higher than that of unshorn animals challenged at room temperature. When the body temperatures of shorn animals are elevated by exposure to elevated environmental temperature, the febrile response and LD50 of endotoxin are restored to levels characteristic of unshorn animals. LSD augments the lethal action of endotoxin even in shorn, hypothermic rabbits. Increased metabolic activity of central vaso-motor and thermoregulatory loci may accompany pyrogenesis. Perhaps such loci are increasingly susceptible to endotoxin as their metabolic activity increases.