Sex-related differences in fever development of rats

Lipopolysaccharide (LPS) or partially purified endogenous pyrogen (EP) was injected intravenously into rats of both sexes to induce fever. In LPS fever, which was easily produced in 24-h dehydrated rats with an intravenous injection of LPS, the female rats showed an attenuated febrile reaction as measured by both the maximum increase of rectal temperature (Tre) and the thermal response index (TI). Although castrated female rats showed the same magnitude of febrile reaction to that in normal female rats, castrated male rats had less of a febrile response than normal male rats. During EP fever, the maximum increase of Tre and TI between the male and female rats was also observed to be different. However, castration of rats of both sexes did not affect the febrile reaction to intravenous injection of EP. Ten-week-old female rats, treated by a subcutaneous injection of testosterone propionate on the 1st day after birth, produced a similar magnitude of febrile reaction to that in the normal male rats that were comparable in age. It is concluded that there are sex-related differences in fever development, due both to EP production and structural sexual differences in the central nervous system pathways regulating fever.