Mediators of the ocular inflammatory response to interleukin-1 beta plus tumor necrosis factor-alpha.
Mediators of the ocular inflammatory response to interleukin-1 beta plus tumor necrosis factor-alpha.
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对白细胞介素 1 β 和肿瘤坏死因子 α 的眼部炎症反应的介质。
DOI：
10.1007/bf00241479
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
McGahan,C
中科院分区：
文献类型：
--
作者：
Fleisher,L;Ferrell,J;McGahan,C
·背景：玻璃体内注射少量炎症剂量的白细胞介素-1 β和肿瘤坏死因子-α（IL-1 β/TNFα）可引起眼内炎症，与玻璃体内注射较高剂量的IL-1或TNFα所引起的眼内炎症明显不同。由于环氧合酶抑制剂和血小板活化因子（PAF）受体拮抗剂可以减少IL-1 β或TNFα诱导的葡萄膜炎，本研究旨在确定花生四烯酸和PAF的环氧合酶代谢产物是否是IL-1β/TNFα诱导的葡萄膜炎的重要介质。研究方法：使用环氧合酶抑制剂吲哚美辛和两种结构不同的PAF受体拮抗剂SRI 63-441和WEB 2086来研究环氧合酶代谢产物和PAF在IL-1β/TNFα诱导的葡萄膜炎中的重要性。结果如下：根据吲哚美辛的有效性，IL-1β/TNFα诱导的前葡萄膜炎可分为两个阶段：依赖于环氧合酶代谢产物产生的初级阶段（前24 h）和基本上不依赖于环氧合酶代谢产物产生的次级阶段（24-48 h）。后葡萄膜炎在48小时也很明显，并通过吲哚美辛减轻。SRI 63-441在24 h时减少了前葡萄膜炎，在48 h时减少程度较小;在48 h时也减少了后葡萄膜炎。然而，尽管WEB 2086在体外减少PAF诱导的血小板聚集方面与SRI 63-441一样有效，但它并没有显著减少IL-1β/TNFα诱导的葡萄膜炎。结论：尽管这些发现不支持PAF在TNF α/IL-1β诱导的葡萄膜炎中的重要作用，但不能排除使用特异性和长效PAF受体拮抗剂进行更强化的治疗可能会产生更积极的结果。
• Background: Intravitreal injection of marginally inflammatory doses of interleukin-1β and tumor necrosis factor-α (IL-1 β/TNFα) has been shown to produce intraocular inflammation distinctly different from that induced by higher intravitreal doses of either IL-1 or TNFα. Since cyclooxygenase inhibitors and platelet-activating factor (PAF)-receptor antagonists can reduce IL-1- or TNFα-induced uveitis, the present investigation was undertaken to determine whether cyclooxygenase metabolites of arachidonic acid and PAF are important mediators of IL-1β/TNFα-induced uveitis.• Methods: The cyclooxygenase inhibitor indomethacin and two structurally dissimilar PAF-receptor antagonists, SRI 63-441 and WEB 2086, were used to investigate the importance of cyclooxygenase metabolites and PAF in IL-1β/TNFα-induced uveitis.• Results: Based upon the effectiveness of indomethacin, the anterior uveitis induced by IL-1β/TNFα could be divided into two phases; a primary phase dependent upon generation of cyclooxygenase metabolites (the first 24 h) and a secondary phase largely independent of cyclooxygenase metabolite production (24–48 h). Posterior uveitis was also apparent at 48 h and was reduced by indomethacin. SRI 63-441 reduced the anterior uveitis at 24 h and to a lesser extent at 48 h; it also reduced the posterior uveitis at 48 h. However, although WEB 2086 was as effective as SRI 63-441 in reducing PAF-induced platelet aggregation, ex vivo, it did not significantly reduce IL-1β/TNFα-induced uveitis.• Conclusions: Although the findings do not support an important role for PAF in TNFa/IL-1β-induced uveitis, it cannot be ruled out that more intensive treatment with a specific and long-acting PAF-receptor antagonist might yield more positive results.