Immunological changes in human blood and skeletal muscle in response to physical exercise

Abstract

Physical exercise is essential for maintaining normal function of skeletal muscle. Muscle tissue also has a remarkable capacity for adaptation to changes in physical demand. In fact, without stimulation from physical activity, muscle tissue will atrophy. The mechanisms responsible for increases or decreases in muscle function are to a large extent not known. According to current opinions, one consequence of physical exercise can be muscle cell damage and inflammation. The inflammatory process is suggested to be one mechanism for muscle adaptation to exercise. Direct evidences for exercise-induced muscle inflammation in humans are weak. Nevertheless, the immune system seems to be of great importance for muscle adaptation. The capacity of the muscle tissue to adapt is largely due to the existence of satellite cells and local growth factors, but the exact molecular mechanism has not been discovered. An interaction between known and yet undiscovered factors are most likely involved m the adaptation process. Physical exercise will also change the number, activation and function of circulating leukocytes. Some of these changes are mediated via adhesion molecules, cytokines, growth factors and hormones.

The purpose of this thesis was to investigate interactions between immunological variables in human blood and skeletal muscle, in conjunction with physical exercise. The main hypothesis was that after physical exercise, circulating leukocytes will migrate to the affected muscle tissue as part of the inflammatory response. Upon completion of the damage-repair-adaptation process they will disappear from the muscle via migration or apoptosis. The magnitude of the inflammatory response should be intensity dependent.

A majority of the subjects who participated in the studies were healthy males. Three different modes of eccentric exercise were used as a model to induce muscle inflammation and in one study immunological changes in the blood of soccer players during training and competition were investigated. Blood and muscle samples were taken before and at various time points after exercise. Immunohistochemical analyses of muscle sections, and blood analyses by flow cytometry, were the main tools used to assess immunological variables. The main findings were: 1) Exercise- induced muscle inflammation could not be observed in human skeletal muscle, 2) The muscle biopsies induced significant skeletal muscle inflammation, 3) HGF and its receptor c-Met, which are important for satellite cell activation, were expressed only in Type 1 skeletal muscle fibers.

It is concluded that the measured immune response to physical exercise is highly individual and depends on exercise mode and duration as well as which variables are analyzed, A significant inflammation in muscle tissue is not a likely result of physical exercise and delayed onset muscle soreness is not caused by muscle or epimysium inflammation. Furthermore, the inflammatory reaction in skeletal muscle is not depressed after strenuous eccentric physical exercise, indicating persisting normal immune function. The observed immunological events m blood and skeletal muscle in relation to physical exercise suggest a complex communication system between the two compartments. Finally, based on the observed effects of physical exercise on healthy muscle one may conclude, that physical exercise should not be precluded from the treatment of patients with inflammatory muscle diseases due to fear of increased muscle inflammation as exercise by itself does not seem to cause an inflammation in muscle tissue.