Effects of the Janus Kinase Inhibitor CP-690550 (Tofacitinib) in a Rat Model of Oxazolone-Induced Chronic Dermatitis
Effects of the Janus Kinase Inhibitor CP-690550 (Tofacitinib) in a Rat Model of Oxazolone-Induced Chronic Dermatitis
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DOI：
10.1159/000347184
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发表时间：
2013-01-01
期刊：
影响因子：
3.1
通讯作者：
Sengoku, Takanori
中科院分区：
文献类型：
--
作者：
Fujii, Yasutomo;Sengoku, Takanori
CP-690550（托法替尼），一种新的Janus激酶（JAK）抑制剂，在慢性过敏性皮炎的影响进行了评价。通过重复应用恶唑酮在大鼠耳中诱导变应性接触性皮炎。这种皮炎伴有持续的耳肿胀和明显的表皮增生。在诱导的耳中，大量炎性细胞浸润到真皮部位，并且干扰素（IFN）-γ、肿瘤坏死因子（TNF）-α和白细胞介素（IL）-22的量升高。CP-690550经口给药可显著抑制耳肿胀和表皮增厚，10 mg/kg剂量的作用与环孢菌素A和依那西普相当。这些结果表明CP-690550（一种JAK抑制剂）作为治疗以表皮增生为特征的慢性皮炎（在其发病机制中IFN-γ、TNF-α和IL-22起作用）如银屑病和慢性特应性皮炎的巨大潜力。版权所有（C）2013 S. Karger AG，巴塞尔
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)-gamma, tumor necrosis factor (TNF)-alpha, 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-gamma, TNF-alpha and IL-22 play a role) such as psoriasis and chronic atopic dermatitis. Copyright (C) 2013 S. Karger AG, Basel