IL-lB and Meal Patterns: Ovarian Hormones and CCK

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DESCRIPTION (provided by applicant): Interleukin (IL-1) is a cytokine that is released by monocytes and macrophages activated during the acute phase response soon after infection or injury. IL-1 is responsible for many of the responses to inflammation and also induces a constellation of symptoms known as sickness behavior" (e.g., malaise, fatigue, decreased eating and drinking, lack of interest in usual activities; Hart, 1988). When administered to rats and mice, IL-1 causes profound alterations in behavior including a suppression of food and water intake (Kent et al., 1995). Previous research provides strong evidence for sex differences in immune function and its modulation by gonadal steroids, indicating that in both human and nonhuman animals females are immunologically stronger then males (Homo-Delarche et al., 1991). Consistent with these observations is the finding that the behavioral responsiveness of female rats to IL-1 is influenced by ovarian hormones (Butera et al., 2001). In this report, the anorectic effects of IL-1 were greater in estradiol-treated ovariectomized females than in untreated controls. Similar findings have also been reported for the febrile response following peripheral treatment with IL-1 (Mouihate et al., 1998). These data indicate that the effects of IL-1 in female rats are influenced by estradiol and suggest that interactions between gonadal steroids and cytokines may contribute to sex differences in the immune response. The general goals of this proposal are to further characterize this endocrine-immune interaction by examining the effects of IL-1 Beta on spontaneous meal patterns during the rat estrous cycle. Examining changes in the microstructure of feeding behavior will provide a better understanding of the ways in which ovarian hormones and IL-1 interact with direct controls of eating (Smith, 2000) to produce the changes in food intake previously observed. The research will evaluate a potential physiological mechanism for these effects on food intake by examining the role of endogenous CCK in estrogen/IL1 interactions. The role of IL-1 in the normal control of food intake will also be evaluated by determining whether changes in endogenous IL-1 contribute to the decrease in food intake that occurs during the proestrus phase of the rat estrous cycle. Information obtained from these experiments will not only contribute to our understanding of how cytokines and gonadal steroids influence ingestive behavior, but will also illustrate how interactions between the endocrine and immune systems may contribute to sex differences in the immune response and disease anorexia.