Biochemical Mechanisms to Explain Immunosuppression in Well-Trained and Overtrained Athletes

Abstract

Glutamine is utilized at a high rate by some cells of the immune System (including lymphocytes and macrophages) and is essential for the viability and normal functioning of these cells. Experiments on lymphocytes in vitro showed that the proliferative response of these cells was dependent on the concentration of glutamine and this suggests that a decrease in plasma glutamine concentration could be responsible, at least in part, for the reported impairment of immune function in various conditions. Much of the glutamine that enters the body is utilized by cells of the small intestine, so that muscle is an important source for the plasma glutamine, Hence, the plasma concentration of glutamine represents a “metabolic link” between skeletal muscle and cells of the immune system. Indeed, the flux-generating step of glutamino metabolism in cells of the immune system is considered to be located in skeletal muscle which synthesizes and stores glutamine. The flux generating step is probably the outward transport of glutamine across the plasma membrane. The rate of this transport process and therefore glutamine release from muscle is decreased in conditions associated with a reduction in immune function or activity in the rat such as sustained exercise. The plasma glutamine concentration in man is decreased in a number of pathological conditions, with the largest decrease recorded following major burns. It is also decreased after prolonged exercise (e.g. marathon run) and in the overtrained state. It is suggested, therefore, that sustained physical activity could damage the glutamine release process so that it does not respond adequately to increased glutamine requirement by the immune system. The plasma glutamine level therefore decreases resulting in an impairment of the function of the immune system.

Alternatively since long chain fatty acids inhibit mitogen-stimulated lymphocyte proliferation and since unsaturated fatty acids caused greater inhibition than saturated fatty acids, this allows another explanation for immunosuppression in the overtrained state to be proposed. These effects of polyunsaturated fatty acids are seen with cells obtained from a variety of sources including rat lymph nodes, spleen, thymus or thoracic duct and human peripheral blood or tonsils. T-cell proliferation was more sensitive to the inhibitory effects of fatty acids than B-cell proliferation. In prolonged exercise, changes in the composition of fatty acids available for immune cells could influence their ability to respond to an immune challenge. Further work is needed to test this hypothesis.

Key words

Glutamine - lymphocytes - muscle - unsaturated fatty acids - exercise