IL-17A-OVA疫苗对实验性自身免疫性葡萄膜炎的影响

 目的 研究IL-17A-OVA多肽疫苗对于实验性自身免疫性葡萄膜炎（EAU）的影响。设计 实验研究。 研究对象  30只C57BL/6小鼠。方法  制备IL-17A-OVA疫苗。将30只C57BL/6小鼠随机分为疫苗组、佐剂组及环孢素组3组，每组10只，佐剂组及疫苗组提前免疫小鼠，第10周时三组小鼠同时用光感受器间维生素A类结合蛋白（IRBP）诱发EAU动物模型。环孢素组造模成功后环孢素连续灌胃2周。HE染色观察小鼠眼球活组织切片，ELISA方法检测小鼠血清中IL-17A、IL-17A特异性抗体、IL-6及IL-23水平。主要指标 小鼠血清中IL-17A、IL-17A特异性抗体、IL-6及IL-23水平。结果 组织病理学显示疫苗组、环孢素组与佐剂组组织病理学评分均有显著性差异（佐剂组评分较高），疫苗组与环孢素组组织病理学评分无显著性差异；血清中IL-17A水平疫苗组（25.785±4.677 pg/ml）与环孢素组（23.129±3.940 pg/ml）均较佐剂组（33.774±6.478 pg/ml）显著降低（F=8.125，P=0.003）；IL-17A特异性抗体水平疫苗组（106.379±12.603 pg/ml）较环孢素组（59.431±8.626 pg/ml）及佐剂组（56.712±4.214 pg/ml）显著升高（F=63.008，P=0.000），环孢素组与佐剂组无显著性差异；血清中IL-6水平疫苗组（41.124±4.959 pg/ml）与环孢素组（29.418±3.34 7 pg/ml）均较佐剂组（49.329±8.768 pg/ml）显著降低（F=18.603，P=0.000）；IL-23水平环孢素组（73.492±12.324 pg/ml）较佐剂组（109.770±20.848 pg/ml）及疫苗组（100.893±13.467 pg/ml）显著降低，疫苗组与佐剂组无显著性差异（F=4.916，P=0.018）。结论 IL-17A-OVA疫苗可通过产生IL-17A特异性抗体在减轻EAU的炎性反应中起到一定的作用，该疫苗可能成为自身免疫性葡萄膜炎治疗的新方法。（眼科，2017，26： 34-38）

Influence of IL-17A-OVA vaccine to experimental autoimmune uveoretinitis

Objective To investigate the influence of IL-17A-OVA vaccine to experimental autoimmune uveoretinitis (EAU). Design Experimental study. Participants Thirty C57BL6 mouses. Methods To produce  IL-17A-OVA vaccine. Thirty C57BL6 mouses were equally divided into adjuvant group, vaccine group and Cyclosporine (CsA) group at random. The first two groups were immunized by IL-17A-OVA or adjuvant firstly. Then EAU with interphotoreceptor retinoid-binding protein (IRBP) in the tenth week was induced. The latter group induced EAU firstly and then given CsA by intragastric administration for 2 weeks. Eyeball biopsy of mouse was observed with HE staining two weeks after EAU induction. IL-17A, IL-17A IgG, IL-6, IL-23 in the serum was measured with ELISA. Main Outcome Measures IL-17A, IL-17A IgG, IL-6 and IL-23 levels in mouse serum. Results HE staining shows that there were significant difference in histopathological score not only between adjuvant group and vaccine group, but also between adjuvant group and CsA group, there was no significant difference between vaccine group and CsA group. IL-17A of vaccine group and Cyclosporine group were significantly lower than adjuvant group (adjuvant group, 33.774±6.478 pg/ml; vaccine group , 25.785±4.677 pg/ml; CsA group, 23.129±3.940 pg/ml ; F=8.125, P=0.003). IL-17A IgG of vaccine group was higher than adjuvant group and CsA group, there was no significant difference between CsA group and adjuvant group(adjuvant group, 56.712±4.214 pg/ml; vaccine group, 106.379±12.603 pg/ml; CsA group, 59.431±8.626 pg/ml ; F=63.008, P=0.000). IL-6 of vaccine group and CsA group were significantly lower than adjuvant group (adjuvant group, 49.329±8.768 pg/ml ; vaccine group, 41.124±4.959 pg/ml; CsA group, 29.418±3.347 pg/ml; F=18.603, P=0.000). IL-23 of CsA group was significantly lower than vaccine group and adjuvant group, there was no significant difference between vaccine group and adjuvant group (adjuvant group, 109.770±20.848 pg/ml; vaccine group, 100.893±13.467 pg/ml; CsA group, 73.492±12.324 pg/ml; F=4.916, P=0.018). Conclusions IL-17A-OVA vaccine has infulunce in reducing the expression of EAU inflammation by the means of IL-17A IgG passway, and may be a new treatment to autoimmune uveitis. (Ophthalmol CHN, 2017, 26: 34-38)