Chemokines in idiopathic inflammatory myopathies

The idiopathic inflammatory myopathies (IIM) represent a heterogeneous group of acquired muscle diseases. The three best-studied subgroups: dermatomyositis (DM), polymyositis (PM), and sporadic inclusion body myositis (IBM), differ considerably both clinically and pathophysiologically. DM is a chiefly humoral endotheliopathy often associated with characteristic skin manifestations. In PM and IBM nonnecrotic muscle fibers are invaded by auto-aggressive cytotoxic T-cells and macrophages. IBM presents with additional structural abnormalities of myofibers, including rimmed vacuoles and depositions of ectopic proteins. Data accumulates implicating the chemokines in the immunopathogenesis of the different IIM. This review bundles current knowledge of the chemokine and chemokine receptor expression in the skeletal muscle of DM, PM and IBM patients. The IIM are characterized by a general increase of specific chemokines, while the chemokine distribution reflects the two different immune responses represented within these muscle diseases: (I) The endotheliopathy of DM is characterized by increased levels of CXCL12 and CCL2 in the affected blood vessels, (II) In the myocytotoxic immune response of PM and IBM, active invasion of nonnecrotic myofibers by inflammatory cells is associated with CXCL10 and CCL2 upregulation. The ever accumulating data illustrates the important role of the chemokine system in IIM, indicating the therapeutic potential of interfering agents. This raises hopes for future treatments for DM and PM with fewer side effects, and the possible establishment of a therapy suited for IBM, a myopathy which has proven unresponsive to all available immuno-modulating interventions up till now.