title: Effects of the Janus kinase inhibitor CP-690550 (tofacitinib) in a rat model of oxazolone-induced chronic dermatitis.
abstract: The effect of CP-690550 (tofacitinib), a new Janus kinase (JAK) inhibitor, was evaluated in chronic allergic dermatitis. Allergic contact dermatitis was induced in rat ears by repeated application of oxazolone. This dermatitis was accompanied by sustained ear swelling and marked epidermal hyperplasia. In the induced ear, a lot of inflammatory cells infiltrated into the dermis site and the amounts of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-22 were elevated. Orally administered CP-690550 significantly suppressed ear swelling as well as epidermal thickening, and the effect at 10 mg/kg was comparable to that of cyclosporin A and etanercept. These results suggest a great potential of CP-690550, a JAK inhibitor, as a treatment for chronic dermatitis featuring epidermal hyperplasia (in the pathogenesis of which IFN-γ, TNF-α and IL-22 play a role) such as psoriasis and chronic atopic dermatitis.
authors.affiliation: Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Japan. yasutomo.fujii@astellas.com
authors.forename: Yasutomo
authors.initials: Y
authors.lastname: Fujii
authors.forename: Takanori
authors.initials: T
authors.lastname: Sengoku
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D016207:Cytokines / Q000276:immunology; D017449:Dermatitis, Allergic Contact / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology / Q000473:pathology; D004423:Ear; D005260:Female; D006965:Hyperplasia / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology / Q000473:pathology; D053612:Janus Kinases / Q000037:antagonists & inhibitors; D010081:Oxazolone; D010880:Piperidines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D010880:Piperidines; D011743:Pyrimidines; D011758:Pyrroles; D010081:Oxazolone; C479163:tofacitinib; D053612:Janus Kinases