Although many cytokines recruiting and priming neutrophils and monocytes were secreted and functional after exhaustive exercise, overwhelming antioxidant and antiinflammatory defenses were induced, preventing exercise-induced oxidative stress.

We analyzed adaptation mechanisms regulating systemic inflammatory response of the stressed body by using an experimental challenge of repeated exercise bouts and accompanying muscle inflammation. Eight untrained men bicycled at 90 W for 90 min, 3 days in a row. Exercise induced peripheral neutrophilia with a leftward shift of neutrophil nucleus and neutrophil priming for oxidative activity determined by luminol-dependent chemiluminescence. Plasma growth hormone and interleukin-6 rose significantly after exercise and were closely correlated with the neutrophil responses. Serum creatine kinase and myoglobin levels as muscle damage markers rose after exercise in "delayed onset" and were closely correlated with the preceding neutrophil responses. These exercise-induced responses were strongest on day 1, but the magnitude gradually decreased with progressive daily exercise. In contrast, the magnitude of catecholamine responses to exercise sessions gradually rose, possibly suppressing neutrophil oxidative responses. These results indicate that stress-induced systemic release of bioactive substances may determine neutrophil mobilization and functional status, which then may affect local tissue damage of susceptible organs.

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.

We examined the hypothesis that the short, intensive exercise-induced increase in circulating neutrophil counts is affected by the interaction between the endocrine and immune systems. Twelve male winter-sports athletes underwent a maximal exercise test on a treadmill. Blood samples were collected before, immediately after (Post), and 1 h (Post 1 h) and 2 h (Post 2 h) after the exercise. The neutrophil counts increased significantly at Post 1 h ( P < 0.05) and remained significantly high even at Post 2 h ( P < 0.05), showing a leftward shift. Plasma granulocyte colony-stimulating factor (G-CSF) increased at Post ( P < 0.05), and interleukin-6 (IL-6) increased at Post 1 h ( P < 0.05). Plasma G-CSF at Post significantly correlated with the numbers of both neutrophils and stab cells at Post 1 h ( P < 0.05). Plasma IL-6 at Post 1 h levels also correlated significantly with the number of neutrophils at Post 2 h ( P < 0.05). The increase in the levels of plasma G-CSF and IL-6 after intensive exercise may play a role in the mobilization of neutrophils into the circulatory system.