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


CONCLUSIONS
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.
Efthimiou
Petros
P
Division of Allergy, Immunology, and Rheumatology, Department of Medicine, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA. efthimpv@umdnj.edu
D006801:Humans; D009220:Myositis / Q000188:drug therapy* / Q000209:etiology* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000502:physiology*
D014409:Tumor Necrosis Factor-alpha