Further observations on the suppression of fever in rabbits by intracerebral action of anisomycin.

Abstract

SUMMARY1. Anisomycin has been given into the cerebral ventricles of rabbits. The inhibitory action ofa range ofdoses on fever and on [14C]leucine incorporation into hypothalamic protein has been studied.2. Fever was far less sensitive to inhibition by anisomycin than was incorporation of ['4C]leucine. The dose-response curves showed a general similarity in shape, which would be compatible with the hypothesis that protein synthesis may be necessary for the production of fever. 3. A comparison was made of the effects of giving anisomycin into the cerebral ventricles 0, 30 or 60 min after the intraventricular injection of leucocyte pyrogen. Anisomycin inhibited fever to some extent even when given 60 min after leucocyte pyrogen. This suggests that if protein synthesis is involved in fever, it may continue at least into the early phase of rising temperature, but probably not to any significant extent after the plateau has been reached.

Inhibition, by trichothecene antibiotics, of brain protein synthesis and fever in rabbits.

“…DDAC and T-2 toxin inhibited fever and were effective in preventing the uptake of leucine into hypothalamic protein. The relative order of magnitude of inhibition of fever on the one hand, and inhibition of ['4C]leucine incorpration on the other, was similar to that demonstrated for anisomycin (Cranston, Hellon & Townsend, 1982), as Fig. 4 shows.…”

“…They are anisomycin (Cranston et at. 1980(Cranston et at. , 1982Ruwe & Myers, 1980), cycloheximide , DDAC and T-2 toxin (this paper).…”

“…Relationship between percentage inhibition of protein synthesis and percentage inhibition of febrile response (see Methods). 0 = results for six different doseb of anisomycin(Cranston et al 1982). 0 = DDAC; A = DAHT; LI = T-2 toxin.…”

“…However, Stitt (1979) demonstrated that cycloheximide, given systemically, rendered rabbits incapable of maintaining their core temperatures when exposed to cold, with the implication that cycloheximide was probably interfering in a non-specific way with the effector mechanisms concerned in pyrogenesis. Since then, we have observed Cranston, Hellon & Townsend, 1980, 1982 that cycloheximide and another protein synthesis inhibitor, anisomycin, given into the cerebral ventricles, can inhibit the febrile response to leucocyte pyrogen (LP) also 448 M. CANNON AND OTHERS given intraventricularly. In the doses given, these two inhibitors were shown not to affect thermoregulation against cold.…”

Macrophage Inflammatory Protein‐1β and Inducible Nitric Oxide Synthase Immunoreactivity in Rat Brain during Prostaglandin E2‐ or Lipopolysaccharide‐Induced Fevera

“…However, much experimental evidence has failed to support the necessity of a PGE in the pathogenesis of fever 4–9 . In fact, a fever produced by a leucocyte pyrogen or pyrogenic cytokine such as IL‐8 or MIP‐1 is unaffected by a pharmacological inhibitor of PGE 2 activity 6,10–13 . Consequently, these and earlier experimental observations do not support the proposition that the synthesis of a PGE or its release in the brain constitutes a fundamental requisite for fever 2,5,9 …”