Is prostaglandin E the neural mediator of the febrile response? The case against a proven obligatory role.

We have reviewed the evidence in favor of a prostaglandin mediator of the thermal responses in fever and found that PGE injected into the hypothalamus does not always cause fever, that cerebrospinal fluid concentrations of PGE are not reliable reflections of hypothalamic events, and that antipyretic drugs may act in ways other than inhibiting PGE synthesis. Fever is not blocked by prostaglandin antagonists, nor by ablation of PGE-sensitive areas of the brain. There is poor correlation between the effects of pyrogens and of PGE on cerebral neurons.

Pig interleukin 1. Purification of two immunologically different leukocyte proteins that cause cartilage resorption, lymphocyte activation, and fever.

Two forms of interleukin 1 (IL-1) were purified to homogeneity from the culture supernatants of pig buffy coat leukocytes stimulated with concanavalin A. The two proteins had identical Mr of 21,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but one, which had previously been purified as a cartilage-resorbing protein, had pI 5 (IL-1/5) and the other, pI 8.3 (IL-1/8).

Naloxone does not influence a pyrogen fever in rabbits.

Rabbits were made febrile by an intravenous injection of homologous endogenous pyrogen (Interleukin 1). When naloxone (0.1 mg/kg i.

Inhibition of brain protein synthesis suppresses the release of prostaglandin E2 in febrile rabbits.

In rabbits the third cerebral ventricle was perfused using a push-pull cannula. Prostaglandin E2 concentration in the perfusate was measured by radioimmunoassay. Prostaglandin concentration rose during fever induced by an intraventricular injection of endogenous pyrogen.

Intraventricular injections of drugs which inhibit phospholipase A2 suppress fever in rabbits.

Injection of two chemically dissimilar inhibitors of phospholipase A2 (mepacrine and parabromophenacylbromide) into the cerebral ventricles of rabbits inhibited the febrile response to endogenous pyrogen given by the same route. 2. The same doses of the inhibitors given intravenously did not affect the febrile response to endogenous pyrogen given into the ventricles, indicating that their action was central.