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The skeletal muscle arachidonic acid cascade in health and inflammatory disease

Key Points

  • Skeletal muscles produce prostaglandins and leukotrienes that control multiple steps of myogenesis, and are critical for skeletal muscle development, growth and repair

  • Prostaglandins and leukotrienes are powerful mediators of inflammation; many pathological conditions in skeletal muscle are associated with altered prostaglandin and leukotriene production

  • NSAIDs or glucocorticoids that suppress prostaglandin production can have adverse effects on the recovery of the muscle strength of patients with polymyositis or dermatomyositis

  • The cyclooxygenase and arachidonate 5-lipoxygenase pathways, involved in the synthesis of prostaglandins and leukotrienes, are enhanced by inflammatory myopathies and might contribute to muscle atrophy, impairment, and pain

  • Fine-tuning of prostaglandin biosynthesis with selective inhibitors of terminal prostaglandin synthases is a viable alternative approach to suppress inflammation in muscle whilst avoiding detrimental effects on muscle repair

Abstract

Muscle atrophy and weakness are often observed in patients with chronic inflammatory diseases, and are the major clinical features of the autoimmune myopathies, polymyositis and dermatomyositis. A general understanding of the pathogenesis of muscle atrophy and the impaired muscle function associated with chronic inflammatory diseases has not been clarified. In this context, arachidonic acid metabolites, such as the prostaglandin and leukotriene subfamilies, are of interest because they contribute to immune and nonimmune processes. Accumulating evidence suggests that prostaglandins and leukotrienes are involved in causing muscular pain and inflammation, and also in myogenesis and the repair of muscles. In this Review, we summarize novel findings that implicate prostaglandins and leukotrienes in the muscle atrophy and weakness that occur in inflammatory diseases of the muscles, with a focus on inflammatory myopathies. We discuss the role of the arachidonic acid cascade in skeletal muscle growth and function, and individual metabolites as potential therapeutic targets for the treatment of inflammatory muscle diseases.

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Figure 1: Biosynthesis of prostaglandins and leukotrienes.
Figure 2: Actions of prostaglandins and leukotrienes in regenerating muscle.
Figure 3: Immunohistochemical staining of skeletal muscle tissue from a patient with polymyositis.

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Acknowledgements

Research by the authors is supported by The Swedish Research Council, The Swedish Rheumatism Association, Karolinska Institutet Foundation, the King Gustaf V 80 year foundation and “The regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet”.

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I. E. Lundberg contributed substantially to the discussion of content and writing, reviewing and editing the manuscript. M. Korotkova researched data for the article, and contributed substantially to discussion of content, and writing, reviewing and editing the manuscript.

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Correspondence to Ingrid E. Lundberg.

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I. E. Lundberg is a stockholder in Pfizer. M. Korotkova declares no competing interests.

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Korotkova, M., Lundberg, I. The skeletal muscle arachidonic acid cascade in health and inflammatory disease. Nat Rev Rheumatol 10, 295–303 (2014). https://doi.org/10.1038/nrrheum.2014.2

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