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白细胞介素-6阻断剂在非感染性葡萄膜炎治疗中的应用

IL-6 blockade in the management of non-infectious uveitis.

作者信息

Lopalco Giuseppe, Fabiani Claudia, Sota Jurgen, Lucherini Orso Maria, Tosi Gian Marco, Frediani Bruno, Iannone Florenzo, Galeazzi Mauro, Franceschini Rossella, Rigante Donato, Cantarini Luca

机构信息

Department of Emergency and Organ Transplantation, Rheumatology Unit, Bari, Italy.

Department of Ophthalmology, Humanitas Clinical and Research Center, Milan, Italy.

出版信息

Clin Rheumatol. 2017 Jul;36(7):1459-1469. doi: 10.1007/s10067-017-3672-z. Epub 2017 May 20.

Abstract

Several pathogenetic studies have paved the way for a newer more rational therapeutic approach to non-infectious uveitis, and treatment of different forms of immune-driven uveitis has drastically evolved in recent years after the advent of biotechnological drugs. Tumor necrosis factor-α targeted therapies, the first-line recommended biologics in uveitis, have certainly led to remarkable results in patients with non-infectious uveitis. Nevertheless, the decision-making process turns out to be extremely difficult in anti-tumor necrosis factor or multidrug-resistant cases. Interleukin (IL)-6 holds a critical role in the pathogenic pathways of uveitis, due to its extended and protean range of effects. On this background, manipulation of IL-6 inflammatory cascade has unraveled encouraging outcomes. For instance, rising evidence has been achieved regarding the successful use of tocilizumab, the humanized monoclonal antibody targeted against the IL-6 receptor, in treating uveitis related to juvenile idiopathic arthritis or Behçet's disease. Similar findings have also been reported for uveitis associated with systemic disorders, such as rheumatoid arthritis or multicentric Castleman disease, but also for idiopathic uveitis, the rare birdshot chorioretinopathy, and even in cases complicated by macular edema. This work provides a digest of all current experiences and evidences concerning IL-6 blockade, as suggested by the medical literature, proving its potential role in the management of non-infectious uveitis.

摘要

多项发病机制研究为非感染性葡萄膜炎开辟了更新、更合理的治疗途径,近年来生物技术药物出现后,不同形式的免疫驱动性葡萄膜炎的治疗方法有了巨大发展。肿瘤坏死因子-α靶向疗法是葡萄膜炎一线推荐的生物制剂,在非感染性葡萄膜炎患者中确实取得了显著疗效。然而,在抗肿瘤坏死因子或多药耐药的病例中,决策过程变得极其困难。白细胞介素(IL)-6因其广泛而多样的作用范围,在葡萄膜炎的发病机制中起着关键作用。在此背景下,对IL-6炎症级联反应的调控已取得了令人鼓舞的成果。例如,越来越多的证据表明,针对IL-6受体的人源化单克隆抗体托珠单抗在治疗与幼年特发性关节炎或白塞病相关的葡萄膜炎方面取得了成功。对于与全身性疾病相关的葡萄膜炎,如类风湿性关节炎或多中心Castleman病,以及特发性葡萄膜炎、罕见的鸟枪弹样脉络膜视网膜病变,甚至是并发黄斑水肿的病例,也有类似的报道。这项工作总结了医学文献中关于IL-6阻断的所有当前经验和证据,证明了其在非感染性葡萄膜炎治疗中的潜在作用。

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