European Journal of Applied Physiology

, Volume 110, Issue 4, pp 797–803 | Cite as

Exhaustive exercise reduces TNF-α and IFN-α production in response to R-848 via toll-like receptor 7 in mice

  • Hiromi Yano
  • Masataka Uchida
  • Ryosuke Nakai
  • Kenji Ishida
  • Yasuko Kato
  • Noriaki Kawanishi
  • Daisuke Shiva
Original Article


Stressful exercise results in temporary immune depression. However, the impact of exercise on the immune responses via toll-like receptor (TLR) 7, which recognizes the common viral genomic feature, single-stranded RNA, remains unclear. To clarify the effect of stressful exercise on immune function in response to viral infection, we measured the changes in the plasma concentration of tumor necrosis factor (TNF)-α and interferon (IFN)-α, which are induced downstream from the TLR–ligand interaction, in exhaustive-exercised mice immediately after treatment with the imidazoquinoline R-848, which can bind to and activate TLR7. Both exhaustive-exercised (EX) and non-exercised (N-EX) male C3H/HeN mice were injected with R-848 (5 mg kg−1), and blood samples were collected. In addition, RAW264 cells, which are mouse macrophage cells, were cultured 30 min after epinephrine (10 μM) or norepinephrine (10 μM) treatments, and were then stimulated with R-848 (10 μg ml−1). In addition, the effect of propranolol (10 mg kg−1) as blockade of β-adrenergic receptors on R-848-induced TNF-α and IFN-α production in the exercised mice was examined. Both the TNF-α and IFN-α concentrations in the plasma of EX were significantly lower than those in the plasma of N-EX after R-848 injection (P < 0.05 and P < 0.01, respectively), although the R-848 treatment increased the plasma TNF-α and IFN-α concentrations in both groups (P < 0.01, respectively). The R-848-induced TNF-α production in RAW264 cells was significantly inhibited by epinephrine and norepinephrine pre-treatment, although IFN-α was not detected. The propranolol treatment completely inhibited exercise-induced TNF-α and IFN-α suppression in response to R-848 in the mice. These data suggest that EX induces a reduction in TNF-α and IFN-α production in response to R-848, and that these phenomena might be regulated by an exercise-induced elevation of the systemic catecholamines.


ssRNA TLR7 Type I interferon Pro-inflammatory cytokine Immune depression C3H/HeN mice 



This work was supported by a Grant-in-Aid for Scientific Research (C-21500700) from the Japan Society for Promotion of Science (JSPS), and the Interdepartmental Research Fund of Kawasaki University of Medical Welfare (to H. Yano).


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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Hiromi Yano
    • 1
  • Masataka Uchida
    • 1
    • 3
  • Ryosuke Nakai
    • 1
  • Kenji Ishida
    • 1
  • Yasuko Kato
    • 2
  • Noriaki Kawanishi
    • 4
  • Daisuke Shiva
    • 5
  1. 1.Department of Health and Sports ScienceKawasaki University of Medical WelfareKurashikiJapan
  2. 2.Department of Clinical NutritionKawasaki University of Medical WelfareKurashikiJapan
  3. 3.Department of Cytology and HistologyOkayama University Graduate School, Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
  4. 4.Graduate School of Sport SciencesWaseda UniversitySaitamaJapan
  5. 5.Department of Health ScienceKurashiki University of Science and the ArtsKurashikiJapan

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