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.

The methyltransferase SMYD3 mediates the recruitment of transcriptional cofactors at the myostatin and c-Met genes and regulates skeletal muscle atrophy

“…Error bars represent SD (n = 3). which are ascribed to myostatin up-regulation (Ma et al 2003;Hanaoka et al 2012). In addition to its role in atrophy, myostatin up-regulation is a hallmark of different forms of muscle wasting, such as sarcopenia (McKay et al 2012), cancer cachexia (Fearon et al 2012;Lokireddy et al 2012), and muscle disuse (Reardon et al 2001).…”

“…Glucocorticoids have broad-spectrum immunosuppressive and anti-inflammatory effects and are thought to be important regulators of muscle mass in catabolic diseases (Hanaoka et al 2012). Nevertheless, extended oversecretion or exogenous administration of glucocorticoids has catabolic effects on skeletal muscle, Figure 6.…”

Glucocorticoids and Skeletal Muscle

“…There are no cures for DMD, but the use of glucocorticoid therapy (prednisone, prednisolone and defl azacort) has been shown to improve muscle strength during the fi rst 6 months of usage followed by stabilization of the course of the disease for up to 2 years, after which there is a decline in function. There are many potential adverse effects of glucocorticoid therapy including osteoporosis, excessive weight gain, and behavioral abnormalities [ 32 ]. While there appear to be short-term benefi ts of glucocorticoid therapy in DMD patients, the long-term functional benefi ts are unclear [ 31 ].…”

The Circadian Clock in Cancer Development and Therapy

“…In vivo , the ANS innervates all peripheral tissues except skeletal muscle through G-protein-coupled transmembrane-receptor (GPCR) in a tissue and/or cell type-specific manner 325–327 . Hormones produced by the pineal gland, HPA and HPG axes, such as melatonin, glucocorticoids, and oestrogen target a wide range of peripheral tissues especially the immune, metabolically active and reproductive organs 328–335 . The rhythmic intracellular signaling generated by neurotransmitters and hormones plays an essential role in maintaining homeostasis of tissue microenvironment (Figure 2).…”