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KMID : 0923620130130060257
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Immune Network
2013 Volume.13 No. 6 p.257 ~ p.263
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CP-690550 Treatment Ameliorates Established Disease and Provides Long-Term Therapeutic Effects in an SKG Arthritis Model
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Oh Keun-Hee
Seo Myung -Won
Kim In-Gyu
Hwang Young-Il
Lee Hee-Yoon
Lee Dong-Sup
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Abstract
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Although pathogenesis of human rheumatoid arthritis (RA) remains unclear, arthritogenic T cells and downstream signal-ing mediators have been shown to play critical roles. An in-creasing numbers of therapeutic options have been added for the effective control of RA. Nevertheless, there is still a category of patients that fails treatment and suffers from progressive disease. The recently developed immunosup-pressant CP-690550, a small molecule JAK kinase inhibitor, has been implicated as an important candidate treatment modality for autoimmune arthritis. In this study, we evaluated the therapeutic effect of CP-690550 on established arthritis using an SKG arthritis model, a pathophysiologically relevant animal model for human RA. CP-690550 treatment revealed remarkable long-term suppressive effects on SKG arthritis when administered to the well-advanced disease (clinical score 3.5∼4.0). The treatment effect lasted at least 3 more weeks after cessation of drug infusion, and suppression of disease was correlated with the reduced pro-inflammatory cytokines, including IL-17, IFN-?, and IL-6 and increased level of immunoregulatory IL-10.
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KEYWORD
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Rheumatoid arthritis, CP-690550, SKG mice, IL-17, IL-10
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