MECHANISM OF STRESS-INDUCED HYPERTHERMIA

有相当多的证据表明，许多急性期反应， 感染是由蛋白质激素白细胞介素-1（IL-1）诱导的。 IL-1 由包括单核细胞在内的多种吞噬细胞分泌， 巨噬细胞以及其他细胞类型如星形胶质细胞、神经胶质细胞 细胞和角质形成细胞。 这种激素（或与之密切相关的一组 激素）诱导许多宿主反应包括发热的发展， 铁和锌的血浆浓度降低， 许多蛋白质如C-反应蛋白，触珠蛋白， 纤维蛋白原和其他，以及许多其他急性期的变化，认为 对受感染的宿主有益 最近，研究表明， 非感染应激、运动也诱导IL-1的释放。 许多研究人员已经表明，暴露于 一个新的环境，如一个开放的领域，结果在一个显着上升， 大鼠的体温 心理压力也与 人的体温升高。 我们已经证明， 一种名为水杨酸钠的药物，可以阻止大部分这种压力引起的体温过高， 大鼠 这些数据向我们表明，这种体温过高的一个组成部分是 实际上是一种真正的发烧，可能是由激素IL-1介导的。 我们提出的第一组实验旨在确定 IL-1是否是造成这种应激诱导的身体内分泌增加的部分原因， 温度 该提案中概述的实验包括表征 在应激诱导的高热期间发生的变化，以确定 是否有其他急性期反应（除了身体的升高， 温度）也由心理压力引起。 我们将尝试 分离并鉴定血液和脑脊液中的IL-1样激素 暴露于空旷场地压力的大鼠的液体，以及 暴露在各种心理压力下的人。 我们还将 试图用抗体来阻止压力引起的温度上升， IL-1。 如果IL-1被证明参与了应激诱导的体内 将使用经典的内分泌/药理学程序 试图确定IL-1升高的机制。

There is considerable evidence that many of the acute phase responses to infection are induced by the protein hormone, interleukin-1 (IL-1). IL-1 is secreted by a variety of phagocytic cells including monocytes and fixed macrophages, as well as by other cell types such as astrocytes, glial cells, and keratinocytes. This hormone (or closely related group of hormones) induces many host responses including the development of fever, reductions in plasma concentration of iron and zinc, elevations in plasma concentrations of many proteins such as C-reactive protein, haptoglobin, fibrinogen, and others, as well as many other acute phase changes thought to be beneficial to the infected host. Recently, it has been shown that a noninfection stress, exercise, also induces the release of IL-1. Many investigators have shown that the psychological stress of exposure to a novel environment, such as an open-field, results in a marked rise in body temperature in rats. Psychological stress is also associated with a rise in body temperature in people. We have shown that the antipyretic drug, sodium salicylate, blocks much of this stress-induced hyperthermia in rats. These data suggest to us that a component of this hyperthermia is actually a true fever, perhaps mediated by the hormone IL-1. The first set of experiments we have proposed are intended to determine whether IL-1 is responsible for part of this stress-induced rise in body temperature. Experiments outlined in this proposal include characterizing the changes that occur during stress-induced hyperthermia to determine whether other acute phase responses (besides the elevation in body temperature) are also induced by psychological stress. We will attempt to isolate and identify an IL-1-like hormone in the blood and cerebrospinal fluid of rats exposed to the stress of an open-field, and in the blood of people exposed to a variety of psychological stresses. We will also attempt to block the stress-induced rise in temperature using antibodies to IL-1. If IL-1 is shown to participate in the stress-induced rise in body temperature, classical endocrine/pharmacologic procedures will be utilized to attempt to determine the mechanism for this rise in IL-1.