Rosenbaum J T, Angell E
Oregon Health Sciences University, Casey Eye Institute, Portland 97201, USA.
J Immunol. 1995 Oct 15;155(8):4090-4.
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.
葡萄膜炎，即眼内炎症，可通过在实验啮齿动物体内局部或全身注射细菌内毒素诱发。内毒素的许多炎症效应可能归因于细胞因子合成的诱导。白细胞介素-10（IL-10）是一种能有效抑制包括IL-1和肿瘤坏死因子-α（TNF-α）在内的多种细胞因子合成的细胞因子。我们评估了IL-10抑制兔和小鼠内毒素诱导的葡萄膜炎的能力。通过房水中细胞和蛋白质积累的减少判断，玻璃体内注射1微克人重组IL-10对兔非常有效，可减轻玻璃体内注射250纳克大肠杆菌内毒素所产生的炎症。在小鼠模型中，局部注射的IL-10在阻断玻璃体内注射内毒素的眼部炎症效应方面同样有效。如果在注射内毒素后延迟注射IL-10，兔模型中炎症效应的减轻程度会降低。与它抑制眼内内毒素局部炎症效应的能力相反，IL-10并没有减轻局部眼内注射400单位人重组IL-α所诱导的炎症。矛盾的是，在腹腔注射内毒素后的葡萄膜炎小鼠模型中，通过组织学切片中所见白细胞数量判断，同时注射1微克IL-10和内毒素会增强眼部炎症。这种效应是剂量依赖性的，因为腹腔注射100微克IL-10可显著抑制眼部炎症。这些观察结果与以下假设相符，即局部注射的IL-10通过减少这些葡萄膜炎模型中的细胞因子合成发挥作用。腹腔注射IL-10可以剂量依赖性方式抑制或减轻内毒素诱导的眼部炎症。
