HYPERRESPONSIVE FEBRILE REACTIONS TO INTERLEUKIN (IL) 1-ALPHA AND IL-1-BETA, AND ALTERED BRAIN CYTOKINE MESSENGER-RNA AND SERUM CYTOKINE LEVELS, IN IL-1-BETA-DEFICIENT MICE

IL-1 beta is an endogenous pyrogen that is induced during systemic lip opolysaccharide (LPS) or IL-1-induced fever, We have examined the feve r and cytokine responses following i.p. injection of IL-1 agonists, IL -1 alpha and IL-1 beta, and compared these with response to LPS (i.p.) in wild-type and IL-1 beta-deficient mice, The IL-1 beta deficient mi ce appear to have elevated body temperature but exhibit a normal circa dian temperature cycle. Exogenously injected IL-1 beta, IL-1 alpha, or LPS induced hyperresponsive fevers in the IL-1 beta-deficient mice, W e also observed phenotypic differences between wild-type and IL-1 beta -deficient mice in hypothalamic basal mRNA levels for IL-1 alpha and I L-6, but not for IL-1 beta-converting enzyme or IL-1 receptor type I o r type II, The IL-1 alpha mRNA levels were down-regulated, whereas the IL-6 mRNA levels were up-regulated in the hypothalamus of IL-1 beta-d eficient mice as compared with wild-type mice, The IL-1 beta-deficient mice also responded to LPS challenge with significantly higher serum corticosterone and with lower serum tumor necrosis factor type alpha l evels than the wild-type mice. The data suggest that, in the redundant cascade of proinflammatory cytokines, IL-1 beta plays an important bu t not obligatory role in fever induction by LPS or IL-1 alpha, as well as in the induction of serum tumor necrosis factor type alpha and cor ticosterone responses either by LPS or by IL-1 alpha or IL-1 beta.