Pathogenesis of idiopathic inflammatory myopathies

Abstract

The idiopathic inflammatory myopathies, myositis, are characterized by a chronic course with decreased muscle endurance and by infiltrates of T lymphocytes and macrophages in muscle tissue. Treatment with immunosuppressives rarely leads to recovery of muscle function, despite abolishment of inflammatory cell infiltrates in muscle tissue. Therefore, other mechanisms than immune-mediated muscle fiber damage are likely to contribute to the pathogenesis. One such non-immune-mediated muscle dysfunction could be caused by a disturbed microcirculation due to capillary loss or to phenotypically changed endothelial cells in the capillaries. These aberrations may affect the micro-environment of muscle tissue and lead to local tissue hypoxia with development of a secondary metabolic myopathy. Another possible non-immune-mediated mechanism leading to muscle dysfunction is the newly identified endoplasmatic reticulum (ER) stress response in myositis. The ER stress response is thought to be a consequence of the up-regulation of major histocompatibility complex class I in muscle fibers. These newly identified molecular pathways could play a major role in the pathogenesis of myositis and could be important targets in the development of new therapies.