Anti-tumor necrosis factor alpha therapy suppresses the induction of experimental autoimmune uveoretinitis in mice by inhibiting antigen priming.
Anti-tumor necrosis factor alpha therapy suppresses the induction of experimental autoimmune uveoretinitis in mice by inhibiting antigen priming.
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发表时间：
1996-10
影响因子：
4.4
通讯作者：
G. Sartani;P. Silver;Luiz V. Rizzo;Chi-Chao Chan;B. Wiggert;George Mastorakos;R. Caspi
中科院分区：
文献类型：
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作者：
G. Sartani;P. Silver;Luiz V. Rizzo;Chi-Chao Chan;B. Wiggert;George Mastorakos;R. Caspi
目的：实验性自身免疫性葡萄膜视网膜炎（EAU）可作为几种影响人眼的免疫介导疾病的模型。先前的研究表明，肿瘤坏死因子α (tnf - α)在EAU中具有重要的促炎作用，可能在人葡萄膜炎中也具有重要的促炎作用。在本研究中，作者研究了抗tnf - α治疗对小鼠EAU的影响。方法B10诱导实验性自身免疫性葡萄膜视网膜炎。光感受器间维甲酸结合蛋白（IRBP）免疫小鼠。用100或300微升兔抗血清或人tnf - α多克隆抗体治疗小鼠。治疗跨越EAU的传入期或传出期（分别为第1、1、3、5、7天或第8、10、12、14、16天）。对照动物在相应时间注射免疫前兔血清或不注射。免疫后3周，通过临床评价和组织病理学对EAU进行评估。通过延迟型超敏反应（DTH）、淋巴细胞对IRBP的增殖和IRBP引发的脾细胞的相对丰度来评估免疫反应。结果兔抗tnf - α血清在输入期可显著改善疾病，而在输出期无明显作用。对DTH、淋巴细胞增殖和抗原反应细胞丰度的影响大致与对疾病的影响相似。结论：中和全身TNF可改善EAU。传入处理的有效性与传出阶段的处理相比，加上irbp应答细胞的增殖减少和丰度降低，表明干扰传入作用过程（如抗原启动）对于通过抗tnf治疗实现对EAU的保护是重要的。
PURPOSE Experimental autoimmune uveoretinitis (EAU) serves as a model for several immune-mediated diseases that affect the eye in humans. Previous studies indicated that tumor necrosis factor alpha (TNF-alpha) has an important proinflammatory role in EAU and possibly in human uveitis. In this study, the authors investigated the effect of anti-TNF-alpha therapy on EAU in mice. METHODS Experimental autoimmune uveoretinitis was induced in B10.A mice by immunization with interphotoreceptor retinoid-binding protein (IRBP). The mice were treated with 100 or 300 microliters rabbit antiserum or polyclonal antibodies to human TNF-alpha. The treatment spanned either the afferent or the efferent stage of EAU (days -1, 1, 3, 5, 7, or days 8, 10, 12, 14, 16, respectively). Control animals were injected with preimmune rabbit serum at the corresponding times or were not treated. Three weeks after immunization, EAU was assessed by clinical evaluation and by histopathology. Immunologic responses were assessed by delayed-type hypersensitivity (DTH), lymphocyte proliferation to IRBP, and relative abundance of IRBP-primed splenocytes. RESULTS The treatment with rabbit anti-TNF-alpha serum significantly ameliorated disease when given during the afferent stage but had no effect when given during the efferent stage of EAU. The effect on DTH, lymphocyte proliferation, and abundance of antigen-reactive cells roughly paralleled the effect on disease. CONCLUSIONS Neutralization of systemic TNF ameliorates EAU. The effectiveness of afferent treatment in comparison to the treatment during the efferent stage, together with the reduced proliferation and the reduced abundance of IRBP-responsive cells, suggest that interference with afferent-acting processes such as antigen priming is important to achieve protection from EAU by anti-TNF treatment.