Sheng W S, Hu S, Lamkin A, Peterson P K, Chao C C
Neuroimmunobiology and Host Defense Laboratory, Minneapolis Medical Research Foundation, and the University of Minnesota Medical School, 55404, USA.
Clin Immunol Immunopathol. 1996 Nov;81(2):161-7. doi: 10.1006/clin.1996.0172.
Proinflammatory cytokines such as interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha have been proposed to play a role in the pathogenesis of fatigue. In the present study we compared the susceptibility of two mouse strains to immunologically induced fatigue. Daily running of two strains of mice, Balb/c and C57BL/ 6, was assessed after a single injection of Corynebacterium parvum antigen (2 mg/mouse). Spontaneous running activity of each animal was compared to mean running distance prior to injection. To evaluate the involvement of cytokines in fatigue development, C57BL/6 mice were treated with antibodies to specific cytokines at the time of challenge with C. parvum antigen. Also, cytokine mRNA expression was analyzed in the brains of mice at different time periods after immunologic challenge. A significant difference in running activity between the two mice strains was observed after C. parvum antigen inoculation: C57BL/6 mice showing a greater (P < 0.05) reduction in running activity (relative to preinjection levels) and slower recovery to baseline than Balb/c mice. Injection of antibodies specific to either IL-1beta or TNF-alpha did not alter immunologically induced fatigue, suggesting a lack of involvement of these cytokines produced outside of the central nervous system (CNS). However, increased TNF-alpha and IL-1beta mRNA expression was found in the brains of C57BL/6 compared to that seen in Balb/c mice at 6, 10, and 15 days after C. parvum antigen injection. The elevated CNS cytokine mRNA expression corresponded to development of fatigue. These findings are consistent with the hypothesis that expression of proinflammatory cytokines within the CNS plays a role in the pathogenesis of immunologically mediated fatigue.
促炎细胞因子如白细胞介素（IL）-1和肿瘤坏死因子（TNF）-α被认为在疲劳的发病机制中起作用。在本研究中，我们比较了两种小鼠品系对免疫诱导疲劳的易感性。在单次注射微小棒状杆菌抗原（2mg/小鼠）后，评估了Balb/c和C57BL/6两种品系小鼠的每日跑步情况。将每只动物的自发跑步活动与注射前的平均跑步距离进行比较。为了评估细胞因子在疲劳发展中的作用，在C. parvum抗原攻击时，用针对特定细胞因子的抗体处理C57BL/6小鼠。此外，在免疫攻击后的不同时间段，分析了小鼠大脑中细胞因子mRNA的表达。在接种C. parvum抗原后，观察到两种小鼠品系的跑步活动存在显著差异：C57BL/6小鼠的跑步活动（相对于注射前水平）下降幅度更大（P < 0.05），且恢复到基线的速度比Balb/c小鼠慢。注射针对IL-1β或TNF-α的特异性抗体并没有改变免疫诱导的疲劳，这表明中枢神经系统（CNS）外产生的这些细胞因子没有参与其中。然而，与Balb/c小鼠相比，在C. parvum抗原注射后6、10和15天，C57BL/6小鼠大脑中TNF-α和IL-1β mRNA的表达增加。中枢神经系统细胞因子mRNA表达的升高与疲劳的发展相对应。这些发现与以下假设一致，即中枢神经系统内促炎细胞因子的表达在免疫介导的疲劳发病机制中起作用。
