Aerobic exercise provokes a systemic cytokine response, including, for example, IL-6, IL-1 receptor antagonist (IL-1ra), and IL-10 (Interleukin 10) and the concentrations of chemokines, IL-8, macrophage inflammatory protein α (MIP-1α), MIP-1β, and MCP-1 rise after vigorous exercise. IL-6 was identified as a myokine based on the observation that it increased in an exponential fashion proportional to the length of exercise and the amount of muscle mass engaged in the exercise. This increase is followed by the appearance of IL-1ra and the anti-inflammatory cytokine IL-10. In general, the cytokine response to exercise and sepsis differs with regard to TNF-α. Thus, the cytokine response to exercise is not preceded by an increase in plasma-TNF-α. Following exercise, the basal plasma IL-6 concentration may increase up to 100-fold, but less dramatic increases are more frequent. The exercise-induced increase of plasma IL-6 occurs in an exponential manner and the peak IL-6 level is reached at the end of the exercise or shortly thereafter. It is the combination of mode, intensity, and duration of the exercise that determines the magnitude of the exercise-induced increase of plasma IL-6.
As studies have demonstrated IL-6 has pro-inflammatory functions when evaluated in regard to sepsis and obesity, it was initially hypothesized that the exercise-induced IL-6 response was related to muscle damage. However, a recent study suggests that eccentric exercise is not associated with a larger increase in plasma IL-6 than exercise involving concentric “nondamaging” muscle contractions. This finding supports the hypothesis that muscle damage is not required to provoke an increase in plasma IL-6 during exercise.
IL-6, among an increasing number of other recently identified myokines, remains an important topic of myokine research. It appears in muscle tissue and in the circulation during exercise at levels up to one hundred times basal rates, as noted, and may have a beneficial impact on health and bodily functioning with transient increases as P. Munoz-Canoves et al. write: "It appears consistently in the literature that IL-6, produced locally by different cell types, has a positive impact on the proliferative capacity of muscle stem cells. This physiological mechanism functions to provide enough muscle progenitors in situations that require a high number of these cells, such as during the processes of muscle regeneration and hypertrophic growth after an acute stimulus. IL-6 is also the founding member of the myokine family of muscle-produced cytokines. Indeed, muscle-produced IL-6 after repeated contractions also has important autocrine and paracrine benefits, acting as a myokine, in regulating energy metabolism, controlling, for example, metabolic functions and stimulating glucose production. It is important to note that these positive effects of IL-6 and other myokines are normally associated with its transient production and short-term action."