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目的 观察抗肿瘤坏死因子-α单克隆抗体(TNF-α MCAb)对于实验性自身免疫性葡萄膜视网膜炎(EAU)的治疗作用.方法 合成光感受器间维生素A类结合蛋白(IRBP)R16多肽片段,联合免疫佐剂诱导EAU动物模型.按照注射次数不同将大鼠分为2组.分别于IRBP R16免疫后的第6天和第4、6、8天自大鼠尾静脉注入TNF-α MCAb,裂隙灯显微镜观察其眼部临床表现,同时设未治疗组大鼠作为对照.于IRBP R16免疫后第13天测量迟发型超敏反应(DTH).并于第14天处死大鼠,取眼球行组织病理检查.应用酶联免疫吸附试验(ELISA)检测抗体注射后14 d时大鼠血清中Th1类细胞因子γ-干扰素(IFN-γ)、Th2类细胞因子白细胞介素-4(IL-4)水平以及房水中IFN-γ水平.测量引流淋巴结细胞的抗原特异性淋巴细胞增生反应.结果 TNF-α MCAb治疗组大鼠的眼部炎症较未治疗组明显减轻,病理分级下降;房水和血清中IFN-γ水平降低,血清中IL-4增高;DTH反应下降;引流淋巴结细胞对IRBP R16多肽刺激的增生反应下降,差异均有统计学意义(P＜0.01).与单次注射相比,3次注射的治疗效果更显著(P＜0.05).结论 TNF-α MCAb能够有效减轻EAU大鼠眼部的炎症反应和特异性细胞免疫反应,改变Th1/Th2细胞因子平衡;多次应用作用更显著.

Objective To observe the efficacy of the anti-tumor necrosis factor-α monoclonal antibody(TNF-α MCAb)in the treatment of experimental autoimmune uveoretinitis(EAU). Methods EAU animal models were induced by interphotoreceptor retinoid-binding protein(IRBP)R16 peptide with immunization.The rats were divided into 2 groups according to the injection times.TNF-α MCAh was administered intravenously on day 6 or 4,6 and 8 post-immunization respectively,and then to observe the clinical expression by slit-lamp microscope.Meanwhile,take the rats which did not accept TNF-α MCAb as conttol group.Delayed type hypersensitivity(DTH)responses were measured on day 13 postimmunization of IRBP R16;the rats were killed on day 14 post-immunization of IRBP R16,and then enucleated the eyes for histopathological examination.To detect the cytokine level of IFN-γ,IL-4 in serum and IFN-γ in aqueous humor by enzyme-liked immunosorbent assay(ELISA)on day 14 postinjection.The hyperplasia responses of antigen specific lymphocyte of draining lymph node cells were detected. Results The TNF-αMCAb group had mitigated ocular inflammation and decreased pathological grades compared with the control group;the IFN-γ concentrations in aqueous humor and serum were decreased,IL-4 was increased in serum;DTH responses were decreased;the hyperplasia responses of draining lymphocytes to IRBP R16 peptide were decreased,all the differences were statistically significant(P＜0.01).The rats accepted TNF-α MCAb thrice had much better curative effect than the rats injected once(P＜0.05). Conclusions Injection of TNF-α MCAb can inhibit ocular inflammation and specific immune cells of EAU remarkably and change the Th1/Th2 balance.Many times injections of TNF-α MCAb were more effective than once.