IL-lB and Meal Patterns: Ovarian Hormones and CCK

描述（由申请人提供）：白细胞介素（IL-1）是一种细胞因子， 由急性期反应期间激活的单核细胞和巨噬细胞释放 感染或受伤后不久。IL-1负责许多反应， 也会引发一系列的症状 行为”（例如，不适，疲劳，饮食减少，缺乏 对日常活动感兴趣;哈特，1988）。当对大鼠和小鼠给药时， IL-1导致行为的深刻改变，包括抑制食物 和水摄入量（肯特等人，1995年）。先前的研究提供了强大的 免疫功能的性别差异及其受性腺调节的证据 类固醇，这表明在人类和非人类动物中， 免疫学上强于雄性（Homo-Delarche等，1991年）。一致 与这些观察结果是发现，行为反应的 雌性大鼠对IL-1的敏感性受卵巢激素的影响（Butera等，2001年）。在 本报告中，IL-1的厌食作用在雌二醇治疗的小鼠中更大。 卵巢切除的女性比未处理的对照组。类似的发现也 据报道，IL-1外周治疗后出现发热反应 （Mouihate等人，1998年）。这些数据表明，IL-1在女性中的作用 大鼠受到雌二醇的影响，并表明性腺之间的相互作用， 类固醇和细胞因子可能导致免疫系统的性别差异， 反应本提案的总体目标是进一步说明这一点， 内分泌-免疫相互作用，通过检查IL-1 β对 大鼠发情周期中的自发进食模式。审查变化， 饲养行为的微观结构将提供更好的理解， 卵巢激素和IL-1相互作用的方式与直接控制 吃（史密斯，2000），以产生先前观察到的食物摄入量的变化。 这项研究将评估这些潜在的生理机制。 通过检测内源性CCK在雌激素/IL 1中的作用， 交互. IL-1在正常控制食物摄入中的作用也将 通过确定内源性IL-1的变化是否有助于 大鼠发情前期食物摄入量减少 发情周期从这些实验中获得的信息不仅 有助于我们理解细胞因子和性腺类固醇如何影响 摄食行为，但也将说明如何之间的相互作用， 内分泌和免疫系统可能导致免疫系统的性别差异， 反应和厌食症。

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.