n South African Journal of Sports Medicine - Interleukin-6 - exercise factor and modulator of metabolic function? : review article




Recent evidence supports multifaceted functions of interleukin- 6 (IL-6). While this cytokine was originally known for its pro-inflammatory function in diseases such as rheumatoid arthritis, today it is recognised for its important antagonistic, anti-inflammatory role in regulating immune processes. Released from skeletal muscle, abdominal adipose and hypothalamic tissue during exercise, it also has 'endocrine-like' metabolic regulatory action that has been linked to energy expenditure, glycogenolysis, and fat oxidation during acute exercise exposure. The quantity and timing of exercise-induced IL- 6 production is dependent on exercise duration, intensity and mode. Eccentric exercise that results in damage to contractile muscle tissue and/or the muscle cytoskeleton, is associated with an increase that peaks approximately 2 hours after cessation of exercise. In contrast, concentric exercise, which is not accompanied by an inflammatory response, induces an increment in IL-6 during exercise. During concentric exercise intramuscular IL-6 production is stimulated by complex signalling cascades which are initiated by elevated intramuscular calcium concentrations. With prolongation of the exercise IL-6 has been shown to act as a 'sensor' regulating blood glucose homeostasis and lipolysis in white adipose tissue. Activation of the IL-6 gene in skeletal muscle is substrate-regulated and greatest when muscle glycogen stores are low. The therapeutic potential of IL-6 in treating obesity has been established in both rodents and humans. While a deficiency of IL-6 has been associated with greater fat mass and lower metabolic rate during exercise, elevated circulating IL-6 concentrations have been shown to inhibit the production of tumour necrosis factor-alpha. This may provide a mechanism to explain how exercise attenuates metabolic disorders associated with low-grade inflammation such as type-2 diabetes, artherosclerosis and possibly autoimmune diseases.


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