Interferon-γ, but Not Interleukin-4, Suppresses Experimental Polymyositis

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Abstract

Objective.

C protein–induced myositis (CIM) is a mouse model of polymyositis in which activated antigen-specific CD8+ T cells injure the muscles. Animal models of autoimmunity that have been examined in the past for the effects of the type 1 cytokine interferon-γ (IFNγ) and the type 2 cytokine interleukin-4 (IL-4) are all mediated by pathogenic CD4+ T cells. In those models, the disruption of IFNγ leads to up-regulation of IL-17A, exacerbating the disease with neutrophil infiltration into sites of inflammation. This study was undertaken to investigate the roles of IFNγ and IL-4, as well as IL-17A in the absence of IFNγ, in CD8+ T cell–mediated CIM.

Methods.

IFNγ−/− mice, anti–IL-17A antibody–treated IFNγ−/− mice, IFNγ−/−IL-17A−/− mice, IL-4−/− mice, and wild-type C57BL/6 mice were immunized with skeletal muscle C protein fragments to induce CIM. Muscle tissue specimens were examined histologically.

Results.

IFNγ−/− mice developed myositis at a higher incidence and with greater severity than wild-type mice. Unlike wild-type mice, IFNγ−/− mice had infiltration of neutrophils into the endomysial sites of the affected muscles. IFNγ−/− mice treated with anti–IL-17A antibodies and IFNγ−/−IL-17A−/− mice developed myositis with an incidence and severity comparable to those in IFNγ−/− mice and showed neutrophil infiltration similar to that in IFNγ−/− mice. IL-4−/− mice developed CIM comparable to that in wild-type mice.

Conclusion.

Our findings indicate that IFNγ, but not IL-4, plays a suppressive role in the development of CIM. Unlike in CD4+ T cell–mediated autoimmune disease models, IFNγ prevents factors other than IL-17A from exacerbating myositis and neutrophil infiltration in CD8+ T cell–mediated CIM.

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