Natural immunity is highly influenced by muscular exercise. Highly consistent changes are found in the production of IL-6 as well as in the number and function of NK cells and neutrophils. During exercise and other physical stress reactions (trauma, surgery, burn) as well as environmental stimuli (hyperthermia and hypoxia), increased catecholamine levels in the circulation induce recruitment of NK cells to the circulation. In response to muscle contractions, IL-6 is produced and released from working skeletal muscles. IL-6 induces increased levels of other anti-inflammatory cytokines such as IL-1 ra and IL-10 and induces Cortisol production and hence suppression of natural killer cell cytotoxicity and neutrophilia. IL-6 also works as an energy sensor. Thus, the production of IL-6 from working muscles is further enhanced if muscle glycogen content is low. In addition, carbohydrate intake during the exercise attenuates the IL-6 production and consequently exercise-induced Cortisol production and fluctuations in NK cells and neutrophils. The major new finding is that exercise-induced immune changes are not a secondary phenomenon to exercise-induced hormonal changes. Rather, muscle contractions per se induce the release of a cytokine, IL-6, which is produced by muscle fibres. By producing IL-6, muscle fibres are directly involved in exercise-induced immune changes, and exercise-induced Cortisol changes can be viewed as a secondary phenomenon, which in turn leads to altered leukocyte subset composition. As IL-6 works as an energy sensor, it is also clear that dietary factors such as carbohydrate may influence the immune response to exercise. It is a hallmark that a cytokine, previously known as a component of the natural immune defence, should now also be viewed as an important player in metabolism.

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