Endotoxin-induced fever is modulated by endogenous glucocorticoids in rats

This study was designed to determine if the febrile response, similar to the inflammatory response, can be modulated by endogenous glucocorticoids. A single intraperitoneal injection of lipopolysaccharide (LPS, 200 micrograms/kg) induced a significant increase in rectal temperature of unrestrained rats maintained within the thermoneutral zone. The febrile response was fully abolished following treatment with a glucocorticoid, dexamethasone (DEX), but was not affected by a mineralocorticoid, deoxycorticosterone acetate (DOCA). Adrenalectomized (ADX) rats were markedly more sensitive to the lethal effects of LPS (200 micrograms/kg), such that all the animals died during the course of the experiment. In addition, ADX rats showed an enhanced febrile response to LPS (10 micrograms/kg ip) in comparison with sham-operated or adrenal-demedullated rats. This enhanced response was reduced by chronic or acute treatment with DEX, but not DOCA. LPS (10 micrograms/kg) also induced a marked rise in plasma corticosterone levels in control rats. In contrast, ADX rats displayed very low plasma corticosterone levels, which were not changed by LPS. In conclusion, the present results reveal that endogenous glucocorticoids are important modulators of LPS-induced fever.