Ophtha-Lab, Department of Ophthalmology at St. Franziskus Hospital, Muenster, Germany.
Invest Ophthalmol Vis Sci. 2013 Jan 2;54(1):39-46. doi: 10.1167/iovs.12-10138.
To investigate the effect of systemic or local TNF-α inhibition with etanercept on experimental autoimmune uveoretinitis (EAU).
EAU was induced by immunizing B10.RIII mice with IRBPp161-180 or by adoptively transferring uveitogenic splenocytes. Mice received systemic or local treatment with etanercept in the afferent or efferent phase. For systemic treatment, mice were injected intraperitoneally. For local treatment, etanercept was injected intravitreally or subconjunctivally. Control mice received PBS. EAU scores were determined histologically. Splenic cells were assessed for [(3)H]thymidine incorporation. ELISA was performed to measure levels of cytokines produced by splenocytes. Vitreous cavity-associated immune deviation (VCAID) was induced by intravitreally injecting ovalbumin and evaluated by measuring DTH reaction.
After systemic treatment with etanercept in the afferent phase, EAU disease scores, IRBP-specific cell proliferation, and production of Th1, Th2, and Th17 cytokines were reduced. EAU also improved after intravitreal etanercept treatment in the afferent phase, with unaltered IRBP-specific proliferation, reduced IFN-γ, but increased IL-6 and IL-10 secretion. VCAID induction was impaired after intravitreal etanercept treatment. No amelioration of EAU or reduction in IRBP-specific cell response was found after systemic or intravitreal treatment in the efferent phase or after subconjunctival treatment. After adoptive transfer, etanercept- and PBS-treated recipients showed similar disease severity and antigen-specific proliferation of splenocytes.
It can be concluded that TNF-α participates mainly in the immunopathology in the induction phase of EAU. The mechanism of action underlying EAU improvement may be different for local and systemic etanercept treatment.
研究依那西普（etanercept）对实验性自身免疫性葡萄膜炎（EAU）的全身或局部 TNF-α 抑制作用。
通过用 IRBPp161-180 免疫 B10.RIII 小鼠或过继转移致葡萄膜炎脾细胞来诱导 EAU。在传入或传出阶段，用依那西普对小鼠进行全身或局部治疗。对于全身治疗，通过腹腔内注射；对于局部治疗，通过玻璃体内或结膜下注射依那西普。对照小鼠接受 PBS。通过组织学确定 EAU 评分。评估脾细胞中 [(3)H]胸苷掺入。通过 ELISA 测量脾细胞产生的细胞因子水平。通过玻璃体内注射卵清蛋白诱导玻璃体腔相关免疫偏离（VCAID），并通过测量迟发型超敏反应来评估。
在传入期用依那西普进行全身治疗后，EAU 疾病评分、IRBP 特异性细胞增殖以及 Th1、Th2 和 Th17 细胞因子的产生减少。传入期玻璃体内给予依那西普治疗后 EAU 也得到改善，IRBP 特异性增殖无改变，但 IFN-γ减少，IL-6 和 IL-10 分泌增加。玻璃体内给予依那西普治疗后 VCAID 诱导受损。在传出期或结膜下治疗后，全身或玻璃体内治疗或结膜下治疗均未发现 EAU 改善或 IRBP 特异性细胞反应减少。过继转移后，依那西普和 PBS 治疗的受者疾病严重程度和脾细胞抗原特异性增殖相似。
可以得出结论，TNF-α 主要参与 EAU 诱导期的免疫病理学。局部和全身依那西普治疗改善 EAU 的作用机制可能不同。
