title: CP-690550 Treatment Ameliorates Established Disease and Provides Long-Term Therapeutic Effects in an SKG Arthritis Model.
abstract: Although pathogenesis of human rheumatoid arthritis (RA) remains unclear, arthritogenic T cells and downstream signaling mediators have been shown to play critical roles. An increasing 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 immunosuppressant 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-γ, and IL-6 and increased level of immunoregulatory IL-10.
authors.affiliation: Laboratory of Immunology, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Korea. ; Department of Anatomy, Seoul National University College of Medicine, Seoul 110-799, Korea. ; Transplantation Research Institute, Seoul National University College of Medicine, Seoul 110-799, Korea.
authors.forename: Keunhee
authors.initials: K
authors.lastname: Oh
authors.affiliation: Laboratory of Immunology, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Korea. ; Department of Anatomy, Seoul National University College of Medicine, Seoul 110-799, Korea.
authors.forename: Myung Won
authors.initials: MW
authors.lastname: Seo
authors.affiliation: Laboratory of Immunology, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Korea.
authors.forename: In Gyu
authors.initials: IG
authors.lastname: Kim
authors.affiliation: Department of Anatomy, Seoul National University College of Medicine, Seoul 110-799, Korea.
authors.forename: Young-Il
authors.initials: YI
authors.lastname: Hwang
authors.affiliation: Department of Chemistry, KAIST, Daejeon 305-701, Korea.
authors.forename: Hee-Yoon
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Laboratory of Immunology, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Korea. ; Department of Anatomy, Seoul National University College of Medicine, Seoul 110-799, Korea. ; Transplantation Research Institute, Seoul National University College of Medicine, Seoul 110-799, Korea.
authors.forename: Dong-Sup
authors.initials: DS
authors.lastname: Lee
keywords: CP-690550; IL-10; IL-17; Rheumatoid arthritis; SKG mice