Exercise-induced immunosuppression: roles of reactive oxygen species and 5'-AMP-activated protein kinase dephosphorylation within immune cells

J Appl Physiol (1985). 2010 May;108(5):1284-92. doi: 10.1152/japplphysiol.00737.2009. Epub 2010 Feb 18.


We previously proposed 5'-AMP-activated protein kinase (AMPK) dephosphorylation within immune cells as an intracellular mechanism linking exercise and immunosuppression. In this study, AMPK phosphorylation underwent transient (<1 h) decreases (53.8+/-7.2% basal) immediately after exercise (45 min of cycling at 70% VO2max) in a cohort of 16 adult male participants. Similar effects were seen with running. However, because exercise-induced inactivation of AMPK was previously shown to occur in an AMP-independent manner, the means by which AMPK is inactivated in this context is not yet clear. To investigate the hypothesis that exercise-induced inactivation of AMPK is mediated via signaling mechanisms distinct from changes in cellular AMP-to-ATP ratios, reactive oxygen species (ROS) and intracellular Ca2+ signaling were investigated in mononuclear cells before and after exercise and in cultured monocytic MM6 cells. In in vitro studies, treatment with an antioxidant (ascorbic acid, 4 h, 50 microM) decreased MM6 cell intracellular ROS levels (88.0+/-5.2% basal) and induced dephosphorylation of AMPK (44.7+/-17.6% basal). By analogy, the fact that exercise decreased mononuclear cell ROS content (32.8+/-16.6% basal), possibly due to downregulation (43.4+/-8.0% basal) of mRNA for NOX2, the catalytic subunit of the cytoplasmic ROS-generating enzyme NADPH oxidase, may provide an explanation for the AMPK-dephosphorylating effect of exercise. In contrast, exercise-induced Ca2+ signaling events did not seem to be coupled to changes in AMPK activity. Thus we propose that the exercise-induced decreases in both intracellular ROS and AMPK phosphorylation seen in this study constitute evidence supporting a role for ROS in controlling AMPK, and hence immune function, in the context of exercise-induced immunosuppression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Antioxidants / pharmacology
  • Ascorbic Acid / pharmacology
  • Bicycling
  • Calcium Signaling
  • Cells, Cultured
  • E-Selectin / blood
  • Exercise*
  • Humans
  • Immune Tolerance* / drug effects
  • Immunoglobulin A / metabolism
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Monocytes / drug effects
  • Monocytes / enzymology*
  • Monocytes / immunology*
  • NADPH Oxidase 2
  • NADPH Oxidases / genetics
  • NADPH Oxidases / metabolism
  • Oxidative Stress* / drug effects
  • Phosphorylation
  • RNA, Messenger / metabolism
  • Reactive Oxygen Species / metabolism*
  • Running
  • Saliva / immunology
  • Time Factors
  • Young Adult


  • Antioxidants
  • E-Selectin
  • Immunoglobulin A
  • Membrane Glycoproteins
  • RNA, Messenger
  • Reactive Oxygen Species
  • CYBB protein, human
  • NADPH Oxidase 2
  • NADPH Oxidases
  • AMP-Activated Protein Kinases
  • PRKAA1 protein, human
  • Ascorbic Acid