白细胞介素-13对内毒素诱导的葡萄膜炎的抑制作用及对局部肿瘤坏死因子-α和白细胞介素-6信使核糖核酸表达的增强作用。

Inhibition of endotoxin-induced uveitis and potentiation of local TNF-alpha and interleukin-6 mRNA expression by interleukin-13.

作者信息

Marie O, Thillaye-Goldenberg B, Naud M C, de Kozak Y

机构信息

INSERM U450, Development, Aging and Pathology of the Retina, Paris, France.

出版信息

Invest Ophthalmol Vis Sci. 1999 Sep;40(10):2275-82.

PMID:10476793

Abstract

PURPOSE

To investigate the effect of systemic injections of interleukin (IL)-13 on the development of endotoxin-induced uveitis (EIU) in the rat.

METHODS

EIU was induced in Lewis rats by a single footpad injection of lipopolysaccharide (LPS; 350 microg/kg) from Salmonella typhimurium. Rats were treated with a subcutaneous injection in the back of recombinant human IL-13 (50 microg/kg in 0.2 ml of saline) performed 30 minutes before LPS injection and 6 and 10 hours afterward. At 23 hours after LPS injection, EIU was evaluated by slit-lamp examination and by counts of inflammatory cells on cryostat sections after specific immunostaining. The expression of nitric oxide synthase (NOS)-II in ocular tissues was determined by dual immunofluorescent staining and the release of nitrite in aqueous humor by Griess reaction. Cytokine gene expression in the iris/ciliary body, choroid, and retina was evaluated by reverse transcription-polymerase chain reaction.

RESULTS

At 24 hours after LPS injection, significant clinical inhibition of ocular inflammation and fibrin deposition in the eye was observed in IL-13-treated rats. Quantitative analysis of ocular tissues revealed a significant decrease of OX42+ cells (microglia, activated macrophages, dendritic cells, and polymorphonuclear leukocytes) and ED-1+ cells (monocytes/macrophages and dendritic cells). No effect on ED2+ cells (resident tissue macrophages) was found. Treatment with IL-13 decreased nitrite levels in aqueous humor and enhanced the expression of tumor necrosis factor-alpha (TNF-alpha) and IL-6 mRNA in ocular tissues.

CONCLUSIONS

Interleukin-13 treatment inhibits LPS-induced ocular inflammation with inhibition of nitrite release and increased TNF and IL-6 production in the eye. These results confirm the role of the NO pathway in the pathogenesis of EIU and suggest the involvement of TNF and IL-6 in the downregulation of ocular inflammation.

摘要

目的

研究全身注射白细胞介素（IL）-13对大鼠内毒素诱导性葡萄膜炎（EIU）发展的影响。

方法

通过在Lewis大鼠的单个足垫注射鼠伤寒沙门氏菌的脂多糖（LPS；350微克/千克）诱导EIU。在LPS注射前30分钟以及注射后6小时和10小时，对大鼠进行皮下注射重组人IL-13（50微克/千克，溶于0.2毫升盐水中）。在LPS注射后23小时，通过裂隙灯检查以及在特定免疫染色后对冰冻切片上的炎性细胞进行计数来评估EIU。通过双重免疫荧光染色测定眼组织中一氧化氮合酶（NOS）-II的表达，并通过格里斯反应测定房水中亚硝酸盐的释放。通过逆转录-聚合酶链反应评估虹膜/睫状体、脉络膜和视网膜中细胞因子基因的表达。

结果

在LPS注射后24小时，观察到IL-13治疗的大鼠眼部炎症和眼内纤维蛋白沉积有明显的临床抑制。对眼组织的定量分析显示，OX42 +细胞（小胶质细胞、活化巨噬细胞、树突状细胞和多形核白细胞）和ED-1 +细胞（单核细胞/巨噬细胞和树突状细胞）显著减少。未发现对ED2 +细胞（驻留组织巨噬细胞）有影响。IL-13治疗降低了房水中亚硝酸盐水平，并增强了眼组织中肿瘤坏死因子-α（TNF-α）和IL-6 mRNA的表达。