T-cells and their cytokine production: The anti-inflammatory and immunosuppressive effects of strenuous exercise

Abstract

Strenuous exercise bouts and heavy training are associated with a heightened anti-inflammatory state and a transient suppression of several immune components. In turn, many athletes are susceptible to illness, particularly upper respiratory symptoms (e.g. cough, sore throat, running nose). T-lymphocytes (T-cells) are important for orchestrating the immune response and can be categorised into subsets according to their phenotypical characteristics resulting from polarisation (i.e. type-1, type-2 and regulatory T-cells). Each T-cell subset has a unique functional role, including their capacity to produce pro- and anti-inflammatory cytokines in response to an immune challenge. Prolonged and exhaustive exercise typically reduces peripheral blood type-1 T-cell number and their capacity to produce the pro-inflammatory cytokine, interferon-γ. Moreover, heavy training loads are associated with elevated numbers of resting peripheral blood type-2 and regulatory T-cells, which characteristically produce the anti-inflammatory cytokines, interleukin-4 and interleukin-10, respectively. This appears to increase the risk of upper respiratory symptoms, potentially due to the cross-regulatory effect of interleukin-4 on interferon-γ production and immunosuppressive action of IL-10. Catecholamines significantly influence the number of peripheral blood T-cells in response to exercise. Whereas, glucocorticoids and prostaglandin E2 promote the production of anti-inflammatory cytokines by T-cells. In summary, strenuous exercise bouts and heavy training shifts T-cell immunity towards an anti-inflammatory state. This impairs the ability of the immune system to mount an inflammatory response to an immune challenge, which may weaken defences against intracellular pathogens (e.g. viruses), and increase the risk of infection and viral reactivation.

Introduction

Athletes are perennially balancing their training load with recovery to optimise performance whilst preventing illness. In contrast to a large proportion of the general population who engage in low-to-moderate levels of physical activity and are at risk of chronic low-grade inflammation, athletes may be susceptible to a heightened anti-inflammatory state. This results from acute and repeated bouts of strenuous exercise, which can transiently suppress immune function and increase the risk of opportunistic infection by viruses and bacteria and viral reactivation. Upper respiratory symptoms (URS) (e.g. cough, sore throat, running nose) are the most commonly reported illness in athletes [1], with recurrent episodes compromising training availability [2] and performance at pinnacle events [3]. T lymphocytes (T-cells) play a pivotal role in the orchestration of the immune response and are currently considered a subclinical immune marker of medium suitability within immunonutrition and exercise investigations [4]. T-cells can polarise into various effector and regulatory cell subsets with divergent functional capacities to eliminate or neutralise pathogens, whilst preventing an overshooting of the immune response to harmless microbes [5]. They mediate other cells of the innate and acquired immune systems by producing specific pro- and anti-inflammatory cytokines [5].

Therefore, the purpose of this narrative review is to describe the effect of strenuous exercise on peripheral blood T-cell subsets and their capacity to produce their signature cytokine. Google Scholar, Scopus and key references from publications were searched using search terms (Exercise, T Lymphocytes, T-cells, cytokines, inflammation, immunity), with no date restriction and only articles in English were considered. Included studies were restricted to exercise at or above 70% VO_2max and/or for periods of 60 min or longer, as well as periods of heavy training, within healthy populations. Furthermore, regulatory factors and the clinical implications of exercise-induced perturbations to T-cell immunity will be explored.