MECHANISMS OF IMMUNOLOGICALLY MEDIATED FATIGUE

疲劳是感染性和自身免疫性疾病的常见临床表现 疾病;它也是慢性病患者的主要投诉 疲劳综合征（CFS）。 免疫过程中产生的细胞因子 激活，已经被假设影响脑细胞功能 导致疲劳。 拟议的工作，这可能是相关的， 为了理解CFS，将测试细胞因子假说， 免疫介导的慢性疲劳 短棒状杆菌全细胞抗原接种模型。 本研究建议的具体目标是：（1）表征 免疫介导的慢性疲劳的小鼠模型（特定目的 （1）;（2）评价所选细胞因子表达与细胞因子表达之间的关联。 小鼠脾和脑组织中的蛋白质含量与慢性疲劳的发生 （具体目标2）;（3）研究已知药物的作用， 抑制细胞因子 产生免疫介导的慢性疲劳（具体目标3）。 对于这些研究，疲劳将通过测量 和持续时间的减少，在自发的日常运行活动， 运动轮跟随整个细胞C.细小病毒抗原接种 C57 BL/6雌性小鼠。 血清细胞因子水平（白细胞介素[IL]-1，IL-6， 转化生长因子-β、干扰素-α与肿瘤坏死 因子-α）和细胞因子mRNA表达 的接种小鼠将与慢性 疲劳 治疗表现出免疫介导的小鼠 用已知抑制细胞因子表达的药物治疗慢性疲劳， 评估其对慢性疲劳发展的影响， 它们在涉及免疫学的疾病中的治疗潜力 介导的疲劳。 这些研究将增强我们对脑梗死的病理生理学的理解。 免疫介导的疲劳，并将促进新的 治疗策略，特别是对CFS患者。

Fatigue is a common clinical manifestation of infectious and autoimmune diseases; it is also the chief complaint of patients with chronic fatigue syndrome (CFS). Cytokines, which are produced during immune activation, have been hypothesized to affect brain cell function resulting in fatigue. The work proposed, which is potentially relevant to und erstanding CFS, will test the cytokine hypothesis of immunologically mediated chronic fatigue using recently developed murine models of whole cell Corynebacterium parvum antigen inoculation. The specific aims of this research proposal are to: (1) characterize a murine model of immunologically mediated chronic fatigue (Specific Aim 1); (2) evaluate the association between selected cytokine expression in splenic and brain tissues of mice and chronic fatigue development (Specific Aim 2); and (3) investigate the effects of drugs known to inhibit cytokine production on immunologically mediated chronic fatigue (Specific Aim 3). For these studies, fatigue will be quantified by measuring the degree and duration of reduction in spontaneous daily running activity on an exercise wheel following whole cell C. parvum antigen inoculation in C57BL/6 female mice. Serum cytokine levels (interleukin [IL]-1, IL-6, transforming growth factor-beta, interferon-alpha, and tumor necrosis factor-alpha) and cytokine mRNA expression in splenic and brain tissues of inoculated mice will be correlated with the development of chronic fatigue. Treatment of mice which display immunologically mediated chronic fatigue with drugs known to inhibit cytokine expression will be performed to assess their impact on development of chronic fatigue and their therapeutic potential in disorders involving immunologically mediated fatigue. These studies will enhance our understanding of the pathophysiology of immunologically mediated fatigue and will foster the development of new treatment strategies, particularly for patients with CFS.