Interleukin-1 production in the brain of febile and stress tolerant rabbits

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Interleukin-1beta (IL-1beta) production in the brain was investigated in rabbits made tolerant to lipopolysaccharide (LPS). The LPS-tolerant rabbits which received intravenous (i.v.) injections of LPS (4 mu g/kg) for five consecutive days showed monophasic fever, the second phase of the LPS (4 mug/kg, i.v.) -induced biphasic fever being disappeared. In situ hybridization and immunohistochemical studies revealed that IL-1beta production was observed in the circumventricular organs, such as the organum vasculosum laminae terminalis (OVLT), 1 h after the first exposure to LPS (acute rabbits). In contrast, IL-1beta production in the OVLT disappeared in the LPS-tolerant rabbits. There was no significant difference in IL-1beta production in spleen between the LPS-injected acute and the LPS-injected tolerant rabbits. These results suggest that the observed changes in IL-1beta production was responsible for the disappearance of second phase of the biphasic fever induced by repeated injections of LPS (febrile tolerance.)