Characteristics of TNF alpha- and TNF beta-induced fever in the rabbit.

Febrile responses of rabbits to recombinant human tumor necrosis factors alpha (TNF alpha) and beta (TNF beta) were compared. Intravenous (0.1-30 micrograms/kg, I.V.) and intracerebroventricular (0.01-2.5 micrograms/kg, I.C.V.) injection of TNF alpha and TNF beta both caused monophasic and biphasic fevers depending on the dose. The magnitude of fever induced by I.V. and I.C.V. injection of TNF beta was significantly greater than that induced by TNF alpha. Moreover, the second peak of TNF beta-induced biphasic fever was attained more quickly than that of TNF alpha-induced fever. Indomethacin given subcutaneously inhibited the fevers produced by I.V. and I.C.V. injection of TNF alpha and TNF beta. Fever induced either by intravenously injected TNF beta or by intracerebroventricularly injected TNF beta was significantly inhibited by I.C.V. pre-injection of indomethacin. On the other hand, indomethacin given intracerebroventricularly did not affect the fever induced by I.V. injection of TNF alpha or that induced by I.C.V. injection of TNF alpha. These results suggest that TNF alpha and TNF beta act on the brain sites responsible for the activation of prostaglandin synthesis in somewhat different ways.