A new murine model to define the critical pathologic and therapeutic mediators of polymyositis
✍ Scribed by Takahiko Sugihara; Chiyoko Sekine; Takashi Nakae; Kuniko Kohyama; Masayoshi Harigai; Yoichiro Iwakura; Yoh Matsumoto; Nobuyuki Miyasaka; Hitoshi Kohsaka
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- English
- Weight
- 569 KB
- Volume
- 56
- Category
- Article
- ISSN
- 0004-3591
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✦ Synopsis
Abstract
Objective
To establish a new murine model of polymyositis (PM) for the understanding of its pathologic mechanisms and the development of new treatment strategies.
Methods
C protein–induced myositis (CIM) was induced by a single immunization of recombinant human skeletal C protein in C57BL/6 mice, as well as in CD4‐depleted, CD8‐depleted, and mutant mice as controls. Some mice were treated with high‐dose intravenous immunoglobulin (IVIG) after disease induction. Muscle tissues were examined histologically.
Results
In mice with CIM, inflammation was confined to the skeletal muscles. Histologic examination revealed a common pathologic feature of CIM and PM, involving abundant infiltration of CD8 and perforin‐expressing cells in the endomysial site of the injured muscle. Suppression of myositis was achieved by depletion of both CD4 and CD8 T cells. Despite the development of serum anti–C protein antibodies in wild‐type mice, severe myositis was induced in mice deficient in B cells. Induction of myositis was suppressed in interleukin‐1α/β (IL‐1α/β)–null mutant mice, but not in tumor necrosis factor α (TNFα)–null mutant mice. Use of IVIG, a treatment with proven efficacy in PM, suppressed CIM in the subgroup of treated mice.
Conclusion
CIM mimics PM pathologically and clinically. Infiltration of CD8 T cells is the most likely mechanism of muscle injury, and IL‐1, but not B cells or TNFα, is crucial in the development of CIM. IVIG has therapeutic effects in CIM, suggesting that the effects of IVIG are not mediated by suppression of antibody‐mediated tissue injury. This murine model provides a useful tool for understanding the pathologic mechanisms of PM and for developing new treatment strategies.