MECHANISM OF STRESS-INDUCED HYPERTHERMIA

有相当多的证据表明，许多急性时相反应 感染是由蛋白质荷尔蒙白介素1(IL-1)诱导的。白介素1 由包括单核细胞在内的各种吞噬细胞分泌，并固定 巨噬细胞，以及其他类型的细胞，如星形胶质细胞、胶质细胞 细胞和角质形成细胞。这种荷尔蒙(或与之密切相关的一组 激素)诱导许多宿主反应，包括发烧， 血浆中铁和锌的浓度降低，血浆中的浓度升高 多种蛋白质的浓度，如C反应蛋白、结合珠蛋白、 纤维蛋白原等，以及其他许多急性时相变化的思想 对受感染的宿主有利。最近，有证据表明， 非感染性压力、运动也会导致IL-1的释放。 许多研究人员已经表明，暴露在空气中的心理压力 新奇的环境，如开阔的田野，会导致 大鼠的体温。心理压力也与 人的体温升高。我们已经证明了退烧药 药物水杨酸钠在很大程度上阻断了这种应激诱导的体温升高。 老鼠。这些数据向我们表明，这种高热的一个成分是 实际上是一种真正的发烧，可能是由荷尔蒙IL-1介导的。 我们提出的第一组实验是为了确定 IL-1是否是应激引起的机体升高的部分原因 温度。这项提案中概述的实验包括 在应激诱导的体温过高过程中发生的变化 是否有其他急性时相反应(除体内升高外 温度)也是由心理压力引起的。我们将尝试 血液和脑脊液中一种IL-1样激素的分离和鉴定 暴露在开阔地带压力下的大鼠的体液，以及血液中的 暴露在各种心理压力之下的人。我们还将 尝试用抗体阻断压力引起的体温升高 IL-1。如果IL-1被证明参与了应激诱导的体内升高 体温，经典内分泌/药理学程序将被使用 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.