Mo J S, Matsukawa A, Ohkawara S, Yoshinaga M
Department of Pathology, Kumamoto University School of Medicine, 2-2-1, Honjo, Kumamoto, 860-0811, Japan.
Exp Eye Res. 1999 Mar;68(3):333-40. doi: 10.1006/exer.1998.0618.
Intravitreal injection of lipopolysaccharide (LPS) induces leukocyte infiltration and protein leakage into the aqueous humor. In the present study, we investigated the role of IL-8 and MCP-1 and regulation of these chemokines by TNFalpha and IL-1 in LPS-induced uveitis in rabbits. After intravitreal injection of LPS, generation of IL-8 in the aqueous humor showed a biphasic pattern with the first peak at 12 hr and the second one at 24 hr, while MCP-1 was produced in a monophasic pattern and peaked at 24 hr. Immunohistochemistry showed that ciliary epithelial cells and infiltrating leukocytes were the producing cells of IL-8 and MCP-1. Administration of anti-IL-8 IgG suppressed by 66% the peak levels of LPS-induced aqueous neutrophil counts at 24 hr but did not suppress aqueous mononuclear cell counts or protein levels. anti-MCP-1 IgG inhibited aqueous mononuclear cell counts by 41% and protein levels by 28%, but did not inhibit aqueous neutrophil counts. The levels of LPS-induced aqueous IL-8 and MCP-1 at 12 hr were inhibited by anti-TNFalpha mAb but not by an IL-1 receptor antagonist (IL-1Ra), while concentrations of the two chemokines at 24 hr were inhibited by both anti-TNFalpha mAb and IL-1Ra. A combination of anti-TNFalpha mAb and rrIL-1Ra had an additive effect on the 24 hr-chemokine levels and inhibited up to 90% chemokine production. Taken together, our results show that IL-8 mediates neutrophil infiltration, while MCP-1 mediates mononuclear cell infiltration and protein leakage in LPS-induced uveitis in rabbits. Levels of aqueous IL-8 and MCP-1 at 12 hr are regulated by TNFalpha, while levels at 24 hr are regulated by TNFalpha and IL-1.
玻璃体内注射脂多糖（LPS）可诱导白细胞浸润并使蛋白质渗漏到房水中。在本研究中，我们调查了IL-8和MCP-1的作用以及TNFα和IL-1对这些趋化因子在LPS诱导的兔葡萄膜炎中的调节作用。玻璃体内注射LPS后，房水中IL-8的产生呈双相模式，第一个峰值出现在12小时，第二个峰值出现在24小时，而MCP-1以单相模式产生，在24小时达到峰值。免疫组织化学显示，睫状上皮细胞和浸润的白细胞是IL-8和MCP-1的产生细胞。给予抗IL-8 IgG可使LPS诱导的房水中性粒细胞计数在24小时时的峰值水平降低66%，但不抑制房水单核细胞计数或蛋白质水平。抗MCP-1 IgG可使房水单核细胞计数降低41%，蛋白质水平降低28%，但不抑制房水中性粒细胞计数。LPS诱导的房水IL-8和MCP-1在12小时时的水平被抗TNFα单克隆抗体抑制，但不被IL-1受体拮抗剂（IL-1Ra）抑制，而两种趋化因子在24小时时的浓度被抗TNFα单克隆抗体和IL-1Ra均抑制。抗TNFα单克隆抗体和重组IL-1Ra的组合对24小时趋化因子水平具有相加作用，并抑制高达90%的趋化因子产生。综上所述，我们的结果表明，IL-8介导中性粒细胞浸润，而MCP-1介导单核细胞浸润和LPS诱导的兔葡萄膜炎中的蛋白质渗漏。房水IL-8和MCP-1在12小时时的水平受TNFα调节，而在24小时时的水平受TNFα和IL-1调节。
