MECHANISM OF STRESS-INDUCED HYPERTHERMIA

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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.