Authors: Moir, Hannah; Butcher, Lee; Jones, Ken P.; Hughes, Michael G.; Neale, Huw; Jia, Huidong; Al-Ismaily, Zuleikha; Webb, Richard

Source: Applied Physiology, Nutrition, and Metabolism, Volume 33, Number 1, January 2008 , pp. 75-85(11)

Publisher: NRC Research Press

Abstract:

There is much evidence that prolonged intense exercise suppresses the immune system. However, the intracellular biochemical mechanisms linking exercise and immunosuppression remain obscure. The purpose of this study was to investigate the hypothesis that exercise-induced inactivation of 5′AMP-activated protein kinase (AMPK) disrupts individual immune cell function, and thus may be linked to exercise-induced immunosuppression. To confirm AMPK's role in immune cells, AMPK activity was assessed in cultured monocytic Mono Mac 6 (MM6) cells. The effects of single bouts of intense exercise (45 min cycling; 70% VO_{2 max}) on several immune parameters including mononuclear cell AMPK phosphorylation were investigated in 10 male volunteers. In vitro, the mitochondrial ATP synthase inhibitor oligomycin brought about transient decreases in cellular [ATP] (0.41 ± 0.04 pmol/cell to 0.31 ± 0.02 pmol/cell), and activation of AMPKα1 (170.7% ± 31.2% basal) and the glycolytic enzyme inducible phosphofructokinase 2 (iPFK-2) (225.0% ± 46.1% basal), with the latter effects coinciding with recovery from ATP depletion. In contrast, exercise-induced transient (~1 h) decreases in AMPKα1 phosphorylation (64.4% ± 17.6% basal). This AMPK inactivation coincided with comparable transient decreases in other immune parameters (salivary IgA levels, serum cytokine levels, monocyte CD36 expression). Although the brief exercise bout employed here is not sufficient to cause full-fledged immunosuppression, exercise-induced transient decreases in mononuclear cell AMPK activation (as seen in this study) may cause energy depletion within individual immune cells, and therefore have an impact upon their ability to carry out their functions. Thus, we suggest that prolonged, repeated, high-intensity exercise that leads to clinically relevant immunosuppression may do so via AMPK inactivation within immune cells.

Plusieurs études appuient la thèse selon laquelle un exercice intense inhibe le système immunitaire. Cependant, nous ne connaissons pas bien les mécanismes biochimiques intracellulaires qui relient l'exercice physique et l'immunosuppression. Le but de cette étude est de tester l'hypothèse selon laquelle l'inactivation de l'AMPK (« 5′AMP-activated protein kinase ») entrave la fonction immunitaire de la cellule de l'individu à l'effort, ce qui expliquerait l'immunosuppression observée à la suite d'un exercice physique. Pour vérifier le rôle de l'AMPK dans les cellules du système immunitaire, on évalue l'activité de l'AMPK dans une culture de cellules Mono Mac 6 (MM6) monocytaires, on évalue chez 10 hommes volontaires les effets de simples séances d'exercice physique intense (45 min de pédalage à vélo; 70 % VO_{2 max}) sur des variables du système immunitaire dont la phosphorylation de l'AMPK dans les cellules mononucléaires. In vitro, l'oligomycine, inhibiteur de l'ATP-synthase mitochondriale, cause la diminution passagère de la concentration cellulaire d'ATP (de 0,41 ± 0,04 à 0,31 ± 0,02 pmol/cellule) et l'activation de l'AMPKα1 (170,7 % ± 31,2 % du niveau de base) et de l'iPFK-2 (225,0 % ± 46,1 % du niveau de base), une enzyme glycolytique, dont les effets coïncident avec la récupération de la déplétion d'ATP. En revanche, l'exercice physique cause des diminutions passagères (~1 h) de la phosphorylation de l'AMPKα1 (64,4 % ± 17,6 % du niveau de base). L'inactivation de l'AMPK coïncide avec des diminutions passagères semblables dans d'autres variables du système immunitaire, soit de la concentration des immunoglobulines A salivaires (IgA), des cytokines sériques et de l'expression des monocytes CD36. Bien que la simple séance d'exercice physique accomplie ne soit pas suffisante pour causer une importante immunosuppression, la diminution passagère de l'activation de l'AMPK dans les cellules mononucléaires causée par l'exercice physique telle qu'on l'observe dans cette étude pourrait causer la déplétion de l'énergie dans les cellules immunitaires et, de ce fait, entraver leurs fonctions. Nous avançons la thèse selon laquelle un exercice physique de forte intensité, prolongé et répété, cause l'immunosuppression manifeste sur un plan clinique par l'inactivation de l'AMPK dans les cellules immunitaires.

Document Type: Research article

Publication date: 2008-01-01

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• This bimonthly journal has a 30-year history of publishing, first as the Canadian Journal of Sport Sciences, and later as the Canadian Journal of Applied Physiology. It publishes original research articles, reviews, and commentaries, focussing on the application of physiology, nutrition, and metabolism to the study of human health, physical activity, and fitness. The published research, reviews, and symposia will be of interest to exercise physiologists, physical fitness and exercise rehabilitation specialists, public health and health care professionals, as well as basic and applied physiologists, nutritionists, and biochemists.
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