Mechanism of fever induction in rabbits

Abstract

Three exogenous pyrogens (Escherichia coli lipopolysaccharide, synthetic double-stranded RNA, Newcastle disease virus) were compared with respect to their mechanisms of fever induction in rabbits. All inducers stimulated the production of an endogenous pyrogen and prostaglandins of the E group in the blood, and cyclic AMP in the CSF. The concentrations of these compounds were elevated approximately 2-fold as compared to the controls. Independently of the mode of induction, the fever reaction could be prevented by pretreatment with 5 mg of cycloheximide/kg, although the 3 fever mediators were induced as in febrile animals. At least 1 additional fever mediator that is sensitive to a 30-50% inhibition of protein synthesis by cycloheximide is postulated. The comparable reactions of the rabbits after administration of different pyrogens argues for a similar fever mechanism. In contrast to fever induction there was no stimulation of endogenous pyrogen, prostaglandins of the E group, and cyclic AMP in hyperthermia as a consequence of exposure of the animals to exogenous overheating. Hyperthermia could not be prevented by cycloheximide.