Circulating sytokines and hormones with immunosuppressive but neutrophil-priming potentials rise after endurance exercise in humans

Katsuhiko Suzuki, Mutsuo Yamada, Shigeyoshi Kurakake, Noriyoshi Okamura, Kanemitsu Yamaya, Qiang Liu, Satoru Kudoh, Kenji Kowatari, Shigeyuki Nakaji*, Kazuo Sugawara

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

241 Citations (Scopus)


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-1β) and interferon gamma (IFN-γ) concentrations remained unchanged after the marathon. The cytokines IL-12, IFN-α and tumour necrosis factor alpha (TNF-α) 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-β) 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.

Original languageEnglish
Pages (from-to)281-287
Number of pages7
JournalEuropean Journal of Applied Physiology
Issue number4
Publication statusPublished - 2000 Mar
Externally publishedYes


  • Cytokines
  • Exercise
  • Immunology
  • Leucocytes
  • Nitric oxide
  • Stress hormones

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Public Health, Environmental and Occupational Health
  • Physiology (medical)


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