IL-6 Blockade Attenuates the Development of Murine Sclerodermatous Chronic Graft-Versus-Host Disease
IL-6 Blockade Attenuates the Development of Murine Sclerodermatous Chronic Graft-Versus-Host Disease
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DOI：
10.1038/jid.2012.226
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发表时间：
2012-12-01
影响因子：
6.5
通讯作者：
Fujimoto, Manabu
中科院分区：
文献类型：
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作者：
Doanh Le Huu;Matsushita, Takashi;Fujimoto, Manabu
系统性硬化症（硬皮病）是一种结缔组织疾病，其特征是皮肤和内脏器官中过量的细胞外基质沉积。据报道，在人类硬皮病和慢性移植物抗宿主病（cGVHD）患者中血清IL-6水平升高。使用抗IL-6受体mAb（anti-IL-6 R mAb）的IL-6阻断导致一些自身免疫性疾病如类风湿性关节炎和幼年特发性关节炎的病理症状的改善。在这项研究中，我们检查了抗IL-6 R mAb对预防或治疗小鼠硬皮病cGVHD（Scl-cGVHD）的作用。结果发现，Scl-cGVHD小鼠骨髓移植后血清IL-6水平逐渐升高。给予抗IL-6 R mAb可减轻重度Scl-cGVHD和纤维化的发生，并导致CD 4（+）CD 25（+）FoxP 3（+）调节性T细胞增加。然而，用抗IL-6 R mAb治疗已建立的Scl-cGVHD对疾病严重程度没有影响。抗IL-6 R mAb的作用主要被抗CD 25 mAb抑制。总之，我们的结果表明，IL-6在Scl-cGVHD的发病机制中具有重要作用。IL-6阻断可能是预防Scl-cGVHD和治疗cGVHD和硬皮病的有效方法。Journal of Investigative Dermatology（2012）132，2752-2761; doi：10.1038/jid.2012.226; 2012年7月19日在线发表
Systemic sclerosis (scleroderma) is a connective tissue disease characterized by excessive extracellular matrix deposition in the skin and visceral organs. Serum IL-6 levels are reported to be elevated in human scleroderma and chronic graft-versus-host disease (cGVHD) patients. IL-6 blockade using anti-IL-6 receptor mAb (anti-IL-6R mAb) results in amelioration of the pathologic symptoms of some autoimmune diseases such as rheumatoid arthritis and juvenile idiopathic arthritis. In this study, we examined the effects of anti-IL-6R mAb on either prevention or treatment of murine sclerodermatous cGVHD (Scl-cGVHD). We found that serum IL-6 levels in Scl-cGVHD mice gradually increased after bone marrow transplantation. Administration of anti-IL-6R mAb attenuated the development of severe Scl-cGVHD and fibrosis and resulted in an increase in CD4(+)CD25(+)FoxP3(+) regulatory T cells. However, treatment of established Scl-cGVHD with anti-IL-6R mAb showed no effects on disease severity. The effects of anti-IL-6R mAb were mostly inhibited by anti-CD25 mAb. Together, our results indicate that IL-6 has an important role in the pathogenesis of Scl-cGVHD. IL-6 blockade may be an effective approach for preventing Scl-cGVHD and treating cGVHD and scleroderma in humans. Journal of Investigative Dermatology (2012) 132, 2752-2761; doi:10.1038/jid.2012.226; published online 19 July 2012