Role of Myokines in Myositis Pathogenesis and Their Potential to be New Therapeutic Targets in Idiopathic Inflammatory Myopathies

Table 1

Myokines present in idiopathic inflammatory myopathies. In this table, we present the main role and activity of the most important myokines in myositis.

Myokines	Role in myositis
IL-6	(i) Controversial: proinflammatory as cytokine, anti-inflammatory as myokine.; (ii) High level in IIM patients and in vitro studies; harmful [46, 48].; (iii) Mediator of innate and adaptive immune response [27, 28].; (iv) Its production induced by inflammatory cytokines TNF-α, IL-17, IL-1β in myoblasts, in vitro [18, 46], not in IIM, but with possible same effects in IIM.; (v) Blocking IL-6 receptors, positive effect, in vivo study on PM model [45].; (vi) Possible biomarker for DM patients [43].
IL-15	(i) Upregulated in myositis—muscle and serum (DM, PM patients) [61, 62].; (ii) Causes muscle weakness—DM, PM patients [64].; (iii) Closely connected with CD163 macrophages—PM patients and PM in vitro model [65].; (iv) Upregulates MMP-9 expression in PM [65].; (v) Possible promotor of autoimmune inflammation in vivo [67].
IL-18	(i) Implicated in autoimmune diseases [75].; (ii) Localised in inflammatory cells and capillaries in IIM patients [76].; (iii) High serum levels in DM/DM with interstitial lung disease [77, 78] and PM [77].
CXCL10	(i) High level in myositis. His CXCR3 receptor also—in vivo [85]; in sIBM patients [86]; in PM, sIBM, DM patients [87]; in juvenile DM [88].; (ii) Possible promotor of autoimmune inflammation through initiation and maintenance of type 1 T-helper cells [84].; (iii) Possible therapeutic target in adult myositis patients [90].
CCL2, CCL3, CCL4, CCL5	(i) MHC I overexpression leads to CCLs release, in vitro [91].; (ii) CCL2 increased levels in IIM patients [48, 82], including juvenile DM [92].; (iii) CCL3, CCL4—upregulated in IIM [93, 94].; (iv) CCL5—low expression in few inflammatory cells in IIM [93].; (v) CCR1 receptor—in macrophages and endothelial cells in sIBM [93].; (vi) CCR5 receptor—in inflammatory cells invading nonnecrotic muscle fibers in IIM [93].; (vii) CCL2 and CCR2 receptor, high levels in IIM patients [95]
CCL20	(i) Upregulated in the presence of IL-17 and IL-1β in muscle cells—in vitro study and in DM, PM muscular biopsies [45].
Myostatin	(i) Accumulates and associates with aggregates containing Aβ in sIBM patients [108].; (ii) Upregulated in IIM [109].; (iii) Myostatin gene expression attenuated, inhibitors gene expression (follistatin) upregulated in resistance training in IBM [110, 111].
Follistatin	(i) Upregulated in inflammatory diseases [120]. Proposed as an inhibitor of myostatin.; (ii) Follistatin gene transfer to sIBM patients—clinical trial, resulted in an improvement in muscle regeneration [117].; (iii) Follistatin high serum levels concomitant with decreased serum myostatin levels in IIM patients [118].
Decorin	Although studies have been performed on its role as opposed to myostatin in skeletal muscle, there are no studies on IIM pathology regarding decorin.
Osteonectin	(i) Upregulated in IIM and in muscular dystrophies [134].
Insl6	(i) Protect the muscle against IIM development; downregulated in IIM—in vivo study [137].; (ii) Insl6 deficiency resulted in a worsened myositis phenotype—in vivo [137].; (iii) When it is downregulated, inflammatory cytokines expression is increased [137].; (iv) Inhibits the proliferation/activation of T-cells [137].; (v) Reduced in PM and DM patients (Insl6 transcript expression) [137].