Exercise as an anti-inflammatory therapy for rheumatic diseases—myokine regulation

Key Points

  • Persistent systemic inflammation is a typical feature of inflammatory rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus

  • Chronic inflammation predisposes to insulin resistance, dyslipidaemia, endothelial dysfunction, accelerated atherosclerosis and neurodegeneration, and thereby to a network of chronic diseases such as type 2 diabetes mellitus, cardiovascular disease and dementia

  • Disease-specific symptoms and comorbidities might negatively affect mobility, physical activity and physical capacity of patients with inflammatory rheumatic diseases

  • Physical inactivity can cause the accumulation of visceral fat, which, along with comorbidities, might further enhance the development of chronic diseases in a 'vicious cycle' of chronic inflammation

  • During exercise, skeletal muscle produces myokines, which might mediate either a direct anti-inflammatory response with each bout of exercise or improvements in comorbidities, thereby indirectly having anti-inflammatory effects

  • Exercise is no longer thought to aggravate inflammation; rather, physical activity is now advocated as an anti-inflammatory therapy for patients with rheumatic diseases


Persistent systemic inflammation, a typical feature of inflammatory rheumatic diseases, is associated with a high cardiovascular risk and predisposes to metabolic disorders and muscle wasting. These disorders can lead to disability and decreased physical activity, exacerbating inflammation and the development of a network of chronic diseases, thus establishing a 'vicious cycle' of chronic inflammation. During the past two decades, advances in research have shed light on the role of exercise as a therapy for rheumatic diseases. One of the most important of these advances is the discovery that skeletal muscle communicates with other organs by secreting proteins called myokines. Some myokines are thought to induce anti-inflammatory responses with each bout of exercise and mediate long-term exercise-induced improvements in cardiovascular risk factors, having an indirect anti-inflammatory effect. Therefore, contrary to fears that physical activity might aggravate inflammatory pathways, exercise is now believed to be a potential treatment for patients with rheumatic diseases. In this Review, we discuss how exercise disrupts the vicious cycle of chronic inflammation directly, after each bout of exercise, and indirectly, by improving comorbidities and cardiovascular risk factors. We also discuss the mechanisms by which some myokines have anti-inflammatory functions in inflammatory rheumatic diseases.

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Figure 1: The vicious cycle of chronic inflammation.
Figure 2: Skeletal muscle is a secretory organ.
Figure 3: Sepsis and macrophages versus exercise and muscle.


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The authors are grateful to CAPES (process 12824-13-5) and FAPESP (process 2011-24093-2) for financial support. The Centre of Inflammation and Metabolism (CIM) is supported by a grant from the Danish National Research Foundation (DNRF55). The Centre for Physical Activity Research is supported by a grant from Trygfonden. CIM is part of the UNIK Project: Food, Fitness & Pharma for Health and Disease, supported by the Danish Ministry of Science, Technology, and Innovation. CIM is a member of DD2, the Danish Center for Strategic Research in Type 2 Diabetes (the Danish Council for Strategic Research grant numbers 09-067009 and 09-075724). The Copenhagen Muscle Research Centre is supported by a grant from the Capital Region of Denmark.

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Both authors contributed equally to researching data for the article, providing a substantial contribution to discussions of the content, writing the article, and to review and/or editing of the manuscript before submission.

Correspondence to Bente K. Pedersen.

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Benatti, F., Pedersen, B. Exercise as an anti-inflammatory therapy for rheumatic diseases—myokine regulation. Nat Rev Rheumatol 11, 86–97 (2015). https://doi.org/10.1038/nrrheum.2014.193

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