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Since the identification of interleukin (IL)-17 as a T-cell-derived cytokine 15 years ago, the contribution of the T-helper type 17 (Th17) pathway in inducing and maintaining chronic inflammation has been well-established, particularly in rheumatoid arthritis. In addition to the main Th1 profile first suggested to contribute to inflammatory myopathies, the presence in inflamed muscle tissue of myositis of IL-17-producing cells, in association with activated dendritic cells, suggests a local activation of the IL-23-Th17 pathway. IL-17 can act on muscle cells together with proinflammatory cytokines produced by monocytes and innate immunity to amplify the immune response that could lead to muscle destruction. Evidence for activation of the Th17 pathway in myositis lesions and in vitro effects of IL-17 on muscle cells suggest IL-17 as a therapeutic target. Inhibitors of IL-17 have been tested in other inflammatory conditions, but the position of IL-17 inhibition in the treatment of inflammatory myopathies remains to be defined.

The idiopathic inflammatory myopathies (IIM) are systemic autoimmune diseases that have predominant mononuclear inflammatory cell infiltrates in the skeletal muscle. The cells that are typically involved in the pathogenesis of disease are B-lymphocytes, T-lymphocytes, macrophages, dendritic cells, and natural killer cells. However, in addition to these immune cells, cells of nonimmunologic origin, such as myocytes, may be directly involved in the immune response. The local milieu also consists of distinct cytokine and chemokine profiles considered related to type 1 interferon stimulation. Tumor necrosis factor and interleukin 1 are also prominent, proinflammatory cytokines involved in the evolution of IIM. Although the pathologic processes involved in IIM have yet to be fully elucidated, we understand the inflammatory milieu is a model of dynamic flux made of diverse cytokine and chemokine expressions leading to alterations in muscle fiber structure and function.

After background information about pathologic findings, this review focuses on the cytokine response in the pathogenesis of polymyositis and dermatomyositis. Cytokines are important mediators of the immune response and play a key role in these diseases by acting on inflammatory immune cells, muscle cells, and vessel cells. Various cytokines are found in myositis samples, in particular interleukin-1 and tumor necrosis factor-alpha, which are associated with the migration, differentiation, and maturation of inflammatory cells. Recent advances indicate that the muscle cell itself could participate in the inflammatory process. Cytokines promote changes in muscle metabolism resulting in a self-sustaining inflammatory response. Accordingly, cytokines may represent new targets for therapies.