顽固性葡萄膜炎的生物治疗展望

The prospects of the biotherapy for refractory uveitis

非感染性葡萄膜炎是临床常见的一组复发性致盲性眼病。糖皮质激素是主要的治疗药物，而长期使用可出现严重的副作用，部分顽固性患者还需免疫抑制剂辅助治疗。由于葡萄膜炎的发生与CD4＋T淋巴细胞介导的自身免疫功能异常有关，巨噬细胞、淋巴细胞和部分炎症细胞因子参与其发病。利用生物制剂拮抗与葡萄膜炎发生相关的淋巴细胞、细胞因子或细胞因子受体，可以抑制免疫反应和炎性反应损伤，稳定病情或减少病情复发，从而达到治疗顽固性葡萄膜炎的目的。这类生物制剂主要包括抗肿瘤坏死因子饯制剂、白细胞介素受体拮抗剂、细胞毒T淋巴细胞相关抗原4融合蛋白、抗CD20单克隆抗体及干扰素仅等。生物制剂为顽固性葡萄膜炎患者的治疗带来了希望，但是由于临床观察例数较少，缺乏多中心随机化临床试验结果，这些制剂的临床适应证、疗效、安全性以及长期副作用等均有待于进一步观察和研究。本文就近年来生物制剂在葡萄膜炎临床和实验性治疗中的应用前景进行综述。

Noninfectious uveitis is a kind of recurrent autoimmune disease and a major cause of blindness in clinical practice. Cortieosteroids are the conventional medication, but have severe side effects for long-term users, and some refractory patients are treated with immunosuppressive agents. Because the pathogenesis of uveitis is related to the autoimmune imbalance mediated by CD4 ＋ T lymphoeytes. The maerophages, lymphoeytes and some cytokines are involved. The immunomodulatory therapy is targeted to block the lymphocytes, eytokines or their receptors, so as to control the inflammatory damage or minimize the recurrence of the disease. The biological agents include the anti-tmnor necrosis factor agents, interferon- ct, interleukin receptor antagonists, cytotoxic T lymphocyte associated antigen fusion proteins and CD20 chimeric antibody. They bring a hope for the treatment of the patients with refractory uveitis. Because of the limited number of randomized clinical trials and patients, the indications, long-term effects, safety and side effects of these biologics need to be observed. In this article, the experiments and clinical trials of these new biologics for the treatment of uveitis in recent years are reviewed.