Abstract
Idiopathic inflammatory myopathies (IIM) represent a heterogeneous group of autoimmune diseases whose treatment is often a challenge. Many patients, even after immunosuppressive therapy, do not respond to treatment, so new alternatives have been sought for this. Therefore, other signaling pathways that could contribute to the pathogenesis of myositis have been investigated, such as the expression of myokines in skeletal muscle in response to the inflammatory process. In this review, we will refer to these muscle cytokines that are overexpressed or downregulated in skeletal muscle in patients with various forms of IIM, thus being able to contribute to the maintenance of the autoimmune process. Some muscle cytokines, through their antagonistic action, may be a helpful contributor to the disease modulation, and thus, they could represent personalized treatment targets. Here, we consider the main myokines involved in the pathogenesis of myositis, expressing our view on the possibility of using them as potential therapeutic targets: interleukins IL-6, IL-15, and IL-18; chemokines CXCL10, CCL2, CCL3, CCL4, CCL5, and CCL20; myostatin; follistatin; decorin; osteonectin; and insulin-like 6. An interesting topic regarding the complex connection between myokines and noninflammatory pathways implied in IIM has also been briefly described, because it is an important scientific approach to the pathogenesis of IIM and can be a therapeutic alternative to be considered, especially for the patients who do not respond to immunosuppressive treatment.
Highlights
This review aims to examine the most recent studies regarding the presence and role of myokines in inflammatory myopathies
Among the myokines that have been cited in the literature as having a possible role in modulating the pathogenesis of myositis, we will address the following: interleukins (IL-6, IL-15, IL-18), chemokines (CXCL10, CCL2, CCL4, CCL5, CCL20), myostatin, follistatin, decorin, osteonectin, and insulin-like 6
Myostatin signaling pathway was reported to be upregulated in inclusion body myositis (IBM) [109] and an assay to block it was performed through gene therapy using follistatin as a myostatin inhibitor
Summary
This review aims to examine the most recent studies regarding the presence and role of myokines in inflammatory myopathies. We would like to focus the attention on myokines as possible therapeutic targets in idiopathic inflammatory myopathies (IIM), as there are still difficulties in treatment approaches that do not have the expected results yet. In this complex group of diseases, there are overlapped clinical diagnostics, nonresponder patients, or a complicated pathogenesis not elucidated so far. A recent review regarding the new classification criteria of myositis is that of Leclair and Lundberg [4] In these conditions, sometimes it is difficult to put a diagnosis because of heterogeneity presented by this group of diseases, and because of overlapping syndromes. We aim to draw attention to the role of myokines in IIM pathology, as well as to the existence of complex interconnected cellular signaling pathways in which muscle cytokines play an increasingly important role
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