Role of interleukin-6 and interleukin-15 in exercise

Cytokines are key modulators of inflammation, participating in acute and chronic inflammation via a complex and sometimes contradictory network of interactions.1 The cytokines and other peptides that are produced, expressed and released by muscle fibers, and exert autocrine, paracrine or endocrine effects, are classified as myokines. Skeletal muscle contains resident immune cell populations and their abundance and type are altered in inflammatory myopathies, endotoxemia or other different types of muscle injury.2 The interleukins (ILs) correspond to class of cytokines released by numerous body tissues to control and coordinate immune responses. There are several isoforms and the most known is interleukin-6 (IL-6), an early-stage myokine that might play important role in exercise-induced muscular growth. IL-6 was first cloned and characterized in the mid-1980s by several independent groups, by assessing immunoglobulin production and acute-phase protein responses in different cell lines.3 IL-6 is a pleiotropic cytokine associated with the control and coordination of immune responses, inflammation, hematopoiesis, and oncogenesis, which regulates cell growth, survival, and differentiation.4 Skeletal muscle cells are a further important source of IL-6 and this cytokine is detected locally at elevated concentrations in actively contracting muscle fibers and after increased workload. Exercise is known to cause major physiological, hormonal, metabolic, and immunological effects. The resistance training acutely upregulates IL-6 by up to 100fold, and the peak of IL-6 level is reached at the end of the exercise or shortly after, about 30 minutes after the exercise, followed by a rapid decrease towards pre-exercise levels.5 Exercise-induced metabolic stress may further stimulate its production.6,7 However, there is a low interaction between muscle damage and increased levels of IL-6, and studies found a low correlation in the time course of IL-6 and creatine kinase.8,9 Therefore, researchers found that muscle tissues during the contraction are the predominant source of IL-6.5 Thus, muscle damage is not required in order to increase plasma IL-6 during exercise.