Suzuki K, Yamada M, Kurakake S, Okamura N, Yamaya K, Liu Q, Kudoh S, Kowatari K, Nakaji S, Sugawara K
Department of Hygiene, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan.
Eur J Appl Physiol. 2000 Mar;81(4):281-7. doi: 10.1007/s004210050044.
To investigate the mechanisms of exercise-induced immune perturbations, we measured promising immunomodulatory hormones and cytokines in plasma of 16 male marathon runners before and after a competitive 42.195-km race. Interleukin 1-beta (IL-1beta) and interferon gamma (IFN-gamma) concentrations remained unchanged after the marathon. The cytokines IL-12, IFN-alpha and tumour necrosis factor alpha (TNF-alpha) could not be detected even using highly sensitive specific immunoassays, indicating at least that overshooting responses of these cytokines had not occurred after exercise. As mechanisms for the small changes in these cytokines, we demonstrated for the first time a significant rise in concentrations of inhibitory cytokine IL-10 in addition to the immunosuppressive hormone cortisol, although concentrations of IL-4 and transforming growth factor-beta (TGF-beta) were unaffected by the race. Furthermore, concentrations of IL-1 receptor antagonist (IL-1ra) and IL-6, which are negative-feedback inhibitors of cytokine production, increased by more than 100 times. As for humoral mediators of neutrophil mobilization, concentrations of growth hormone (GH), cortisol and granulocyte colony-stimulating factor (G-CSF) increased significantly. In addition, concentrations of neutrophil-priming substances (IL-6, IL-8, G-CSF, GH and prolactin) also increased significantly and the induction of IL-8 and G-CSF with exercise was demonstrated for the first time in the present study. In contrast, IL-2 concentration decreased, by 32%, and this was correlated with the induction of nitric oxide (NO) production. Muscle damage, monitored using changes in concentrations of creatine kinase and myoglobin, was also observed. These results suggested that exercise-induced pathogenesis including previously reported immunosuppression and neutrophil hyper-reactivity might be attributed, at least partly, to the systemic dynamics of the above bioactive substances.
为了研究运动引起的免疫紊乱机制，我们在16名男性马拉松运动员参加42.195公里的竞技比赛前后，测量了他们血浆中具有潜在免疫调节作用的激素和细胞因子。马拉松赛后白细胞介素1-β（IL-1β）和干扰素γ（IFN-γ）浓度保持不变。即使使用高灵敏度的特异性免疫测定法，也无法检测到细胞因子IL-12、IFN-α和肿瘤坏死因子α（TNF-α），这至少表明运动后这些细胞因子没有出现过度反应。作为这些细胞因子微小变化的机制，我们首次证明，除了免疫抑制激素皮质醇外，抑制性细胞因子IL-10的浓度显著升高，尽管IL-4和转化生长因子-β（TGF-β）的浓度不受比赛影响。此外，作为细胞因子产生的负反馈抑制剂，IL-1受体拮抗剂（IL-1ra）和IL-6的浓度增加了100多倍。至于中性粒细胞动员的体液介质，生长激素（GH）、皮质醇和粒细胞集落刺激因子（G-CSF）的浓度显著增加。此外，中性粒细胞启动物质（IL-6、IL-8、G-CSF）、GH和催乳素的浓度也显著增加，并且在本研究中首次证明了运动可诱导IL-8和G-CSF。相比之下，IL-2浓度下降了32%，这与一氧化氮（NO）产生的诱导有关。还观察到了肌肉损伤，通过肌酸激酶和肌红蛋白浓度的变化进行监测。这些结果表明，运动引起的发病机制，包括先前报道的免疫抑制和中性粒细胞高反应性，可能至少部分归因于上述生物活性物质的全身动态变化。
