STRESS-INDUCED FEVER--ROLE OF CYTOKINES AND HORMONES

描述(改编自申请者的摘要)：接触心理社会 压力会使大鼠的体温升高高达2摄氏度。这个 申请人已经生成的数据支持压力的假设 “体温过高”实际上是一种发烧(即体温调节升高 设定点)，由内源性热原和前列腺素引起。细胞因子是 在压力引起的发烧期间释放，申请者发现 将老鼠暴露在新的环境中会导致 炎症和免疫的中介物IL-6的浓度。 预先应用肿瘤坏死因子-α抗血清可导致应激增加 发烧。也有证据表明，去肾上腺的大鼠 更大的应激性发热和血浆IL-6浓度升高 当给予替代皮质酮时，情况正好相反。灌输 RU38486进入下丘脑前部提示糖皮质激素阴性 应激引起的发热和IL-6升高的反馈发生在 中枢神经系统。此外，注射β-肾上腺素能受体 中枢神经系统阻滞剂可同时减轻应激性发热和 IL-6细胞因子。这项研究的目的是：1)确定 β-肾上腺素能受体在调节应激性脑缺血时的作用部位 体温和循环细胞因子；和2)决定作用和 循环糖皮质激素在调节应激反应中的作用部位 体温和循环中的细胞因子升高。

DESCRIPTION (Adapted from applicant's abstract): Exposure to psychosocial stress produces rises in body temperature of as much as 2oC in rats. The applicant has 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 prostanoids. Cytokines are released during stress-induced fevers and the applicant has found that exposing a rat to a novel environment results in an increase in concentrations of IL-6, a mediator of inflammation and immunity. Pretreatment with antiserum to TNF-alpha results in an increase of stress fevers. Evidence is also presented that adrenalectomized rats develop larger stress-induced fevers and increased plasma concentrations of IL-6 which is reversed when replacement corticosterone is given. Infusion of RU38486 into the anterior hypothalamus suggests that glucocorticoid negative feedback on stress induced fever and IL-6 rises occur at the level of the central nervous system. Furthermore, injection of beta-adrenoceptor blockers into the CNS attenuates both stress-induced fevers and the rise of IL-6 cytokines. The aims of this study are to: 1) determine the role and site of action of beta-adrenoceptors in modulating stress-induced rises in body temperature and circulating cytokines; and 2) determine the role and site of action of circulating glucocorticoids in modulating stress-induced rises in body temperature and circulating cytokines.