Febrile responses induced in adrenalectomized rats by administration of interleukin-1 beta or prostaglandin E2

1. The present study was carried out to investigate the effect of bilateral adrenalectomy on fevers induced in rats by systemic injection of interleukin-1 beta (IL-1 beta) or by central injection of prostaglandin E2 (PGE2). 2. Intraperitoneal (I.P.) injections of two doses of IL-1 beta (0.5 and 1.0 microgram kg-1) induced biphasic fevers in normal control rats in a dose-dependent manner. Adrenalectomized (ADX) rats showed higher fevers than sham-ADX rats after I.P. injection of small doses of IL-1 beta (0.5 micrograms kg-1). This fever enhancement was inhibited by acute or chronic glucocorticoid, dexamethasone (DEX), treatment. In contrast, there was no significant difference between fevers induced in ADX and sham-ADX rats by I.P. injection of large doses of IL-1 beta (1.0 g kg-1). 3. Dose-dependent fevers were observed in normal control rats after injections of several doses of PGE2 (5, 25 and 100 ng) into the preoptic hypothalamic area (POA). The injection of a large dose of PGE2 (100 ng) into the POA led to a lower fever in ADX rats, compared with that in sham-ADX rats. This fever in ADX rats was increased by acute or chronic treatment with DEX. On the other hand, adrenalectomy had no effect on fevers induced by the injections of small doses of PGE2 (5 and 25 ng) 4. The injections of PGE2 (100 ng) into the POA induced increases in oxygen consumptions in ADX rats that were significantly smaller than those in sham-ADX rats, suggesting that the lower PGE2 fever was, at least in part, due to attenuated thermogenesis in ADX rats. 5. There was no significant difference in plasma osmolality between the ADX and the sham-ADX rats. The ADX rats were given 0.9% salt water instead of tap water. 6. These results suggest that endogenous glucocorticoid is one of the important modulators of the IL-1-induced and the PGE2-induced fevers in rats.