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Myokines are peptides produced and released by myocytes of muscle fibers that influence physiology of muscle and other organs and tissues. They are involved in mediating the beneficial effects that exercise has on health. More than one hundred have been identified and among them are IL6, myostatin, irisin, mionectin and decorin. Physical inactivity leads to an altered response of the secretion of myokines and resistance to them; this leads to a pro-inflammatory state that favors sarcopenia and fat accumulation, promoting the development of cardiovascular diseases, insulin resistance, and diabetes mellitus type 2. Some myokines, including irisin, are responsible for the improvement that exercise produces in many chronic diseases such as type 2 diabetes and cardiovascular diseases, some types of cancer and many autoimmune diseases such as idiopathic inflammatory myopathy, rheumatoid arthritis, systemic lupus erythematosus and inflammatory bowel disease., (Copyright © 2018 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)