Tumor necrosis factor-alpha in inflammatory myopathies: pathophysiology and therapeutic implications

OBJECTIVES: To present, in an organized fashion, data from the medical literature on the possible role of tumor necrosis factor (TNF)-alpha in the pathogenesis of dermatomyositis (DM) and polymyositis (PM), as well as recent clinical studies where TNF-inhibition was used as a treatment for myositis. METHODS: PUBMED was searched from 1966 to the present using the terms: TNF-alpha, TNF-inhibitors, dermatomyositis, polymyositis, myositis, and inflammatory myopathy. In addition, relevant abstracts from major recent rheumatology meetings were retrieved. RESULTS: Several studies that employed immunostaining and polymerase chain reaction analysis in muscle biopsy specimens from patients with inflammatory myopathies showed increased presence of TNF-alpha and its soluble receptors in inflamed muscle. One genetic study proposed an association between DM and the -308A TNF polymorphism. Abnormally high levels of TNF-alpha in the muscle may be directly toxic to myofibers, while preventing muscle regeneration. Furthermore, TNF-alpha may induce, or augment, the production of other pro-inflammatory cytokines such as interleukin (IL)-1, monocyte chemotactic protein-1, IL-6, and IL-8. These findings have prompted some investigators to use off-label, TNF-inhibitors in DM/PM patients, especially if they had failed corticosteroids, immune gamma-globulin, and traditional immunosuppressive agents. The results from these early, uncontrolled, studies have been promising. CONCLUSION: TNF-alpha may have a role in the pathogenesis of the myositis and has emerged as a possible therapeutic target. Larger, carefully controlled studies are needed to confirm the results from early studies and clearly define the efficacy and safety of anti-TNF agents in the treatment of inflammatory myopathies.