TUMOR NECROSIS FACTOR-INDUCED UVEITIS IN THE LEWIS RAT IS ASSOCIATED WITH INTRAOCULAR INTERLEUKIN-6 PRODUCTION
TUMOR NECROSIS FACTOR-INDUCED UVEITIS IN THE LEWIS RAT IS ASSOCIATED WITH INTRAOCULAR INTERLEUKIN-6 PRODUCTION
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DOI：
10.1016/s0014-4835(95)80011-5
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发表时间：
1995-02-01
影响因子：
3.4
通讯作者：
KIJLSTRA, A
中科院分区：
文献类型：
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作者：
DEVOS, AF;VANHAREN, MC;KIJLSTRA, A
向刘易斯大鼠玻璃体内（0.08-50 ng）或心内（1 μ g）注射重组鼠肿瘤坏死因子-α。裂隙灯检查肿瘤坏死因子诱导的眼内炎症反应，并测定蛋白外渗到房水中。通过免疫组织化学分析眼内炎性细胞的表型。此外，还测定了眼内白细胞介素6产生的动力学。在玻璃体内注射后24小时，与盐水处理的对照组相比，仅在注射50 ng肿瘤坏死因子的大鼠中观察到显著的临床葡萄膜炎（P < 0.05）。最大的临床葡萄膜炎和血-房水屏障破坏已经存在于肿瘤坏死因子注射后4小时。葡萄膜炎的特征是前段大量细胞浸润，主要由多形核细胞和巨噬细胞/单核细胞组成，T淋巴细胞的程度较低。眼内白细胞介素6 mRNA的表达和白细胞介素6在房水中的水平升高后1小时检测到的肿瘤坏死因子注射后，在3至4小时达到最高，并在2小时再次下降。虽然心内注射1微克的肿瘤坏死因子在刘易斯大鼠诱导循环白细胞介素6的上升，它没有产生葡萄膜炎。玻璃体内注射肿瘤坏死因子的结果表明，眼内TNF可能在诱导大鼠葡萄膜炎中发挥关键作用。在肿瘤坏死因子诱导的葡萄膜炎早期，瞬时眼内产生白细胞介素6，表明这种细胞因子可能参与肿瘤坏死因子诱导的反应。
Lewis rats were injected with recombinant murine tumour necrosis factor-alpha either intravitreally (0.08-50 ng) or intracardially (1 mu g). The intraocular inflammatory response induced by tumour necrosis factor was examined by slit-lamp and protein extravasation into aqueous humor was determined. The phenotype of the inflammatory cells in the eye was analysed by immunohistochemistry. In addition, the kinetics of intraocular interleukin 6 production were determined. At 24 hr after intravitreal injection, a significant clinical uveitis was observed only in rats injected with 50 ng of tumour necrosis factor, when compared to saline-treated controls (P < 0.05). Maximal clinical uveitis and blood-aqueous barrier breakdown were already present at 4 hr after tumour necrosis factor injection. The uveitis was characterized by a massive cellular infiltrate in the anterior segment, consisting predominantly of polymorphonuclear cells and macrophages/monocytes, and to a lesser extent of T lymphocytes. Intraocular interleukin 6 mRNA expression and elevated levels of interleukin 6 in aqueous humor were detected 1 hr after tumor necrosis factor injection, reached a maximum at 3 to 4 hr after injection, and had declined again at 2 hr. Although intracardial injection of 1 pg of tumour necrosis factor in Lewis rats induced a rise of circulating interleukin 6, it did not produce uveitis. The results obtained with intravitreally injected tumour necrosis factor indicate that intraocular TNF may play a pivotal role in the induction of uveitis in the rat. The transient intraocular production of interleukin 6 early during tumour necrosis factor-induced uveitis suggests that this cytokine may participate in the response induced by tumour necrosis factor.