Influence of ambient temperature on peripherally induced interleukin-1 beta fever in young and old rats

We have previously demonstrated that old and young rats mount similar fevers after intraperitoneal (i.p.) LPS injection at a warm ambient temperature (Ta) of 31 degrees C, but not at a cooler Ta of 21 degrees C. LPS stimulates the synthesis and release of proinflammatory cytokines, particularly interleukin-1 beta (IL-1 beta), necessary for fever development, and possibly this is attenuated at the lower Ta. If so, then administration of exogenous IL-1 beta should enable old rats to mount fevers equivalent to those of young rats regardless of Ta. Here, young (3-5 months) and old (23-29 months) Long-Evans rats were maintained at Ta 21 or 31 degrees C for 3 days prior to i.p. or intravenous (i.v.) injection of rat recombinant IL-1 beta (1 microg/kg) or vehicle. Three days later, rats were given the alternate injection at the same T(a). At least 5 days later, the same rats were injected at the other Ta. Body temperature was continuously monitored throughout the experiments. Young rats mounted fevers after LPS at both Ta's and i.p. fevers were lower than i.v. fevers. Old rats developed fevers that were equivalent to those of young rats at 31 degrees C regardless of route of administration, but no fever responses were evident at 21 degrees C. These data suggest that the attenuated fever of old rats is not due to an inability to produce IL-1 beta, but rather to a deficiency further along in the fever pathway. In addition, these results show that, as with LPS, Ta plays a role in the ability of old rats to mount fever in response to IL-1 beta.