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Implications of glucocorticoid therapy in idiopathic inflammatory myopathies

Abstract

Glucocorticoids are the cornerstone of therapy in patients with idiopathic inflammatory myopathies (IIM), despite adverse effects and suboptimal therapy success rates. Glucocorticoids are used in patients with IIM to suppress inflammatory and immune responses implicated in the pathogenesis of these diseases. Nevertheless, potential inhibitory effects of glucocorticoids on skeletal muscle mass, myogenesis and immune responses that promote skeletal muscle regeneration after muscle injury warrant attention. Glucocorticoids lead to skeletal muscle catabolism by modulating major pathways involved in regulating muscle mass. Glucocorticoids also inhibit muscle regeneration by decreasing myogenic cell proliferation and differentiation. Finally, glucocorticoids might have inhibitory effects on immune cells that have been shown to be an important component of the muscle regenerative response. Better understanding of the signalling pathways involved in restorative versus adverse effects of glucocorticoids in IIM could yield additional insight into the aetiopathogenesis of persistent muscle weakness in patients with IIM after glucocorticoid treatment, and help in the development of novel, targeted treatment options with fewer adverse effects.

Key Points

  • Glucocorticoids can exert inhibitory effects on skeletal muscle mass, myogenesis and immune responses that alter skeletal muscle regeneration following muscle injury

  • Skeletal muscle catabolism results from glucocorticoid effects on major pathways involved in regulating muscle mass

  • Glucocorticoids also inhibit muscle regeneration by decreasing myogenic cell proliferation and differentiation

  • Immune cells that form an important component of the muscle regenerative response seem to be inhibited by glucocorticoids

  • Understanding signalling pathways that mediate restorative versus adverse effects of glucocorticoids in IIM could provide aetiopathogenic insights into myositis, and innovative targeted treatment options with fewer adverse effects

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Figure 1: Regulation of muscle mass by the IGF-1 pathway.
Figure 2: Interplay between IGF-1 and myostatin signalling in the regulation of muscle mass, and the effects of GCs.
Figure 3: The canonical and noncanonical NFκB pathways in skeletal muscle, and the effects of GCs.
Figure 4: Photomicrographs of CIM and glucocorticoid-induced myopathy.
Figure 5: The effects of glucocorticoids on postnatal skeletal muscle regeneration.

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B. Y. Hanaoka, C. A. Peterson and L. J. Crofford contributed equally to researching data for the article, discussing the content of the article and writing the article. B. Y. Hanaoka, C. A. Peterson, C. Horbinski and L. J. Crofford contributed equally to review/editing of the manuscript before submission.

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Correspondence to Leslie J. Crofford.

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Hanaoka, B., Peterson, C., Horbinski, C. et al. Implications of glucocorticoid therapy in idiopathic inflammatory myopathies. Nat Rev Rheumatol 8, 448–457 (2012). https://doi.org/10.1038/nrrheum.2012.85

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