PSYCHOSOCIAL STRESS-INDUCED FEVER--THE ROLES OF CYTOKINE

暴露于社会心理压力会导致体温升高， 在老鼠体内只有2摄氏度。 香港市民的体温上升 对心理压力的反应也有报道。 心理社会 压力也被证明会改变艾滋病的病程。 过去 几年来，我们已经产生了支持这一假设的数据， 压力“体温过高”实际上是发烧（即，的升高 体温调节设定点），由内源性热原引起， 前列腺素E2 此外，我们已经证明，简单地将大鼠暴露于 新的环境导致等离子体的显著增加， IL-6是炎症和免疫的介质， 用TNF抗血清预处理大鼠（即，TNF α）导致 压力发烧的增加。 我们有兴趣检验的假设是 细胞因子和其他被认为与感染有关的肽 诱导发热（在诱导发热和调节 发烧）（例如，IL-1、TNF、IL-6、PGE 2精氨酸加压素（AVP）和α- MSH）负责应激诱导的体温过高， 不是由内源性阿片类药物引起的 拟议研究的具体目标如下： 1. 为了继续我们对接触小说的影响的研究 环境（大鼠）对血浆IL-6、PGE 2、精氨酸活性的影响 加压素和α-MSH。 2. 测定血浆IL-6、IL-1、TNF、PGE 2、AVP、 而α-MSH则足以影响（增加或减少） 应力引起的温度上升。 3. 为了验证心理压力会导致 IL-1、TNF、IL-6、PGE 2、AVP和α-MSH进入脑脊液，或 大鼠的脑组织。 4. 为了验证心理压力导致 从枯否细胞或循环中自发释放IL-1、TNF或IL-6 应激后分离的血液单核细胞。 5. 为了验证心理压力使枯否细胞或 循环血单核细胞对其他刺激更敏感，如 脂多糖，已知引起IL-1，TNF， 和IL-6 6. 为了检验用抗体或抗体预处理大鼠 针对IL-1、TNF、IL-6、AVP和α-MSH的特异性受体拮抗剂 改变（增加或减少）应激诱导的体温过高。 这些研究可能对了解艾滋病的进展有意义 从潜伏的艾滋病毒感染到全面爆发的疾病， 实验室已经显示IL-6和TNF导致协同诱导 在慢性HIV感染细胞模型中的HIV表达。

Exposure to psychosocial stress produces rises in body temperature of as much as 2 degrees Celsius in rats. Rises in body temperature of people in response to psychological stress have also been reported. Psychosocial stress has also been shown to alter the course of AIDS. Over the past several years we have generated data that support the hypothesis that stress "hyperthermia" is actually a fever (i.e., an elevation in thermoregulatory set-point), caused by endogenous pyrogens and prostaglandin E2. In addition, we have shown that simply exposing a rat to a novel environment results in a significant increase in the plasma concentration of IL-6, a mediator of inflammation and immunity, and that pretreatment of rats with antiserum to TNF (i.e., TNFalpha) results in an increase in stress-fevers. The hypothesis we are interested in testing is that cytokines and other peptides thought to be involved in infection- induced fever (both in inducing fever and modulating the magnitude of the fever) (e.g., IL-1, TNF, IL-6, PGE2 arginine vasopressin (AVP) and alpha- MSH) are responsible for that portion of stress-induced hyperthermia that is not caused by endogenous opioids. The specific aims of the proposed studies are as follows: 1. To continue our investigations on the effects of exposure to a novel environment (in rats) on plasma activity of IL-6, PGE2, arginine vasopressin, and alpha-MSH. 2. To determine whether plasma activities of IL-6, IL-1, TNF, PGE2, AVP, and alpha-MSH are high enough to affect (either increases or decreases) the stress-induced rise in temperature. 3. To test the hypothesis that psychological stress induces the release of IL-1, TNF, IL-6, PGE2, AVP, and alpha-MSH into the cerebrospinal fluid, or brain tissue of rats. 4. To test the hypothesis that psychological stress induces the spontaneous release of IL-1, TNF, or IL-6 from Kupffer cells or circulating blood monocytes isolated following the stress. 5. To test the hypothesis that psychological stress makes Kupffer cells or circulating blood monocytes more sensitive to other stimuli, such as lipopolysaccharide, known to cause the synthesis and release of IL-1, TNF, and IL-6. 6. To test the hypothesis that pretreatment of rats with antibodies or specific receptor antagonists against IL-1, TNF, IL-6, AVP, and alpha-MSH alters (either increases or decreases) stress-induced hyperthermia. These studies may have relevance for understanding the progression of AIDS from latent HIV infection to full-blown disease since studies from another laboratory have shown that IL-6 and TNF results in a synergistic induction of HIV expression in chronically HIV-infected cell models.