Paradoxical effects of IL-10 in endotoxin-induced uveitis.
Paradoxical effects of IL-10 in endotoxin-induced uveitis.
复制标题
IL-10 在内毒素诱导的葡萄膜炎中的矛盾作用。
DOI：
10.4049/jimmunol.155.8.4090
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发表时间：
1995
影响因子：
4.4
通讯作者：
E. Angell
中科院分区：
文献类型：
--
作者：
J. Rosenbaum;E. Angell
葡萄膜炎或眼内炎症可由局部或全身注射细菌内毒素引起。许多内毒素的炎症作用可能是由于诱导细胞因子合成。IL-10是一种细胞因子，能有效抑制多种细胞因子的合成，包括IL-1和tnf - α。我们已经评估了IL-10抑制内毒素诱导的兔和小鼠葡萄膜炎的能力。通过减少房水中细胞和蛋白质的积累来判断，玻璃体内注射1微克人重组IL-10对兔玻璃体内注射250 ng大肠杆菌内毒素产生的炎症非常有效。在小鼠模型中，局部注射IL-10同样有效地阻断玻璃体内注射内毒素的眼部炎症作用。如果在内毒素注射后延迟注射IL-10，兔模型的炎症减轻作用减弱。与IL-10抑制眼部内毒素局部炎症作用的能力相反，IL-10并没有减轻眼部局部注射400 U人重组il - α引起的炎症。矛盾的是，在腹腔注射内毒素后葡萄膜炎的小鼠模型中，同时注射1微克的IL-10和内毒素会增强眼部炎症，这是通过组织学切片中看到的白细胞数量来判断的。这种效果是剂量依赖性的，因为100微克的IL-10注射可显著抑制眼部炎症。这些观察结果与局部注射IL-10通过减少这些葡萄膜炎模型中细胞因子合成而起作用的假设相一致。腹腔注射IL-10可以抑制或抑制内毒素引起的眼部炎症，并呈剂量依赖性。
Uveitis, or intraocular inflammation, can be provoked in laboratory rodents by the local or systemic injection of bacterial endotoxin. Many of the inflammatory effects of endotoxin are potentially due to the induction of cytokine synthesis. IL-10 is a cytokine that potently inhibits the synthesis of many cytokines, including IL-1 and TNF-alpha. We have assessed the ability of IL-10 to inhibit endotoxin-induced uveitis in rabbits and mice. The intravitreal injection of 1 micrograms of human recombinant IL-10 was extremely effective in rabbits in reducing the inflammation produced by the intravitreal injection of 250 ng of Escherichia coli endotoxin, as judged by the reduced accumulation of cells and protein in the aqueous humor. Locally injected IL-10 was similarly effective in blocking the ocular inflammatory effects of intravitreally injected endotoxin in a mouse model. If the injection of IL-10 was delayed subsequent to the endotoxin injection, the reduced inflammatory effects in the rabbit model were diminished. In contrast to its ability to inhibit the local inflammatory effect of endotoxin in the eye, IL-10 did not reduce the inflammation induced by a local ocular injection of 400 U of human recombinant IL-alpha. Paradoxically, in a mouse model of uveitis subsequent to intraperitoneally injected endotoxin, the simultaneous injection of 1 micrograms of IL-10 and endotoxin potentiated the ocular inflammation, as judged by the number of leukocytes seen in histologic sections. This effect was dose dependent, since eye inflammation was markedly inhibited by 100 micrograms of IL-10 injected i.p. These observations are compatible with the hypothesis that locally injected IL-10 acts by reducing cytokine synthesis in these uveitis models. Intraperitoneally injected IL-10 can either inhibit or suppress endotoxin-induced eye inflammation in a dose-dependent manner.