Exhaustive exercise reduces TNF-α and IFN-α production in response to R-848 via toll-like receptor 7 in mice.
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.
Yano
Hiromi
H
Department of Health and Sports Science, Kawasaki University of Medical Welfare, 288 Matsushima, Kurashiki, Okayama, 701-0193, Japan. yanohiro@mw.kawasaki-m.ac.jp
Uchida
Masataka
M
Nakai
Ryosuke
R
Ishida
Kenji
K
Kato
Yasuko
Y
Kawanishi
Noriaki
N
Shiva
Daisuke
D
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D004837:Epinephrine / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D007108:Immune Tolerance / Q000187:drug effects / Q000502:physiology*; D016898:Interferon-alpha / Q000097:blood*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000819:agonists / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D009638:Norepinephrine / Q000494:pharmacology; D005082:Physical Exertion / Q000502:physiology*; D051199:Toll-Like Receptor 7 / Q000819:agonists / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D016898:Interferon-alpha; D008562:Membrane Glycoproteins; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D014409:Tumor Necrosis Factor-alpha; C402365:resiquimod; D009638:Norepinephrine; D004837:Epinephrine