ROS-induced AMPK inactivation in monocytes: A possible mechanism underpinning exercise-induced immunosuppression
Cardiff Metropolitan University
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Introduction: Whilst moderate regular exercise carries an abundance of health benefits including improved immune function, it is well documented that vigorous, prolonged exercise and highly physically demanding training regimes can result in immunosuppression. This is evidenced by the higher incidence of upper respiratory tract infections (URTIs) in athletes. High intensity exercise has been linked to decreases in several immune parameters, but the causes and mechanisms underpinning these decreases remain unknown. Previous studies have linked AMPK to exercise induced immunosuppression. AMP-activated protein kinase (AMPK) is a heterotrimeric complex found in all cells, which plays a key role in maintaining cellular energy status. Its regulation by reactive oxygen species (ROS) is well recognised, as is the effect of exercise on changes in ROS. All cells, including immune cells require sufficient levels of energy to perform cellular functions. Any disruptions in AMPK activity in immune cells could result in an inhibition of immune functions due to an inadequate energy supply. This study investigated this theory in monocytes, due to their roles in both innate and adaptive immunity, as well as in the anti-viral defence important in the defence against URTIs. Methods: 5 active males underwent a prolonged high intensity endurance exercise session (45 minute cycle at 70% VO2 Max). Blood samples were taken before, immediately after, 1.5 hours, 3 hours and 24 hours post exercise. Peripheral monocytes were treated with 2',7'-dichlorofluorescein-diacetate (DCFH) and intracellular levels of reactive oxygen species (ROS) analysed using flow cytometry. Saliva samples were also taken and salivary IgA levels were analysed by ELISA technique as a comparative measure of immune function. Results: Monocyte ROS production decreased immediately after exercise (116.7 ± 102.4nM H2O2 to 81.9 ± 56.9 nM H2O2) and remained decreased until 3 hours post exercise. There was a transient increase at 3 hours post exercise (122.9 ± 80.1 nM H2O2), with a subsequent retum to suppressed levels at24hours post exercise (64.6 + 34.9 nM H2O2). These changes were mirrored by salivary IgA levels, and a significant correlation (P = 0.012) was observed between these 2 variables. Conclusion: It can be concluded from these results that high intensity exercise causes decreases in ROS production in monocytes, which may inactivate AMPK. This may deplete monocyte energy reserves and inhibit monocytic function, contributing to immunosuppression. The reason for the decrease in ROS production in these cells remains to be seen. Further work is required to determine whether the same effect is seen in other immune cells. The precise identity and source of ROS is also an area in need of further investigation.
MSc Biomedical Science
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