THE ROLE OF LIPID A IN ENDOTOXIN-INDUCED UVEITIS

第一部分：脂多糖组和乳酸组的临床对比研究脂多糖组和乳酸组均能成功诱导葡萄膜炎，眼部炎症的高峰分别在1000和100µg/kg。第二部分：LPS和LA组CINC家族的分析用EIA法检测AH组和两组血清中CINC家族浓度的时程变化，发现AH组的CINC-1水平高于LA组。两组大鼠血清CINC-1水平均在6h达到高峰，内毒素组也明显高于对照组。内毒素组的AH比LA组的AH具有更强的趋化活性。在静脉注射重组CINC-1的大鼠中，对AC的细胞渗透的评估表明，CINC-1以剂量依赖的方式抑制炎症细胞向AC的迁移。已有报道，当CINC-1的浓度超过10 ng/mL时，促进中性粒细胞膜上L-选择素的脱落，使中性粒细胞与血管内皮细胞相互作用。因此，在内毒素模型的血管内高水平的CINC-1似乎是一个合理的替代方法来解释低水平的细胞迁移到AC。LA诱导的葡萄膜炎比LPS诱导的葡萄膜炎在眼内引起更多的炎症，而不过度改变全身的内环境平衡。这些发现应作为进一步选择葡萄膜炎模型的参考。

Part I-Comparative clinical study of LPS and LA groupsThe LPS and LA successfully induced uveitis and the peak of the ocular inflammation was obtained with 1000 mug/kg and 100 mug/kg, respectively. Cells in the AC were more numerous in the LA group than the LPS group at any given level of protein concentration.Part II-Analysis of the CINC family in LPS and LA groupsThe time course variation in the CINC family concentration in AH and serum samples obtained from both LPS and LA groups was assessed by EIA.The CINC-1 level in AH showed higher concentration in the LPS group compared to the LA group. The serum level of CINC-1 peaked at 6 hours in both groups and was also significantly higher in the LPS-group. The AH fromthe LPS group possessed stronger chemoattractant activity than the AH from the LA group. The evaluation of the cell infiltration into the AC in the rats injected with intravenous recombinant CINC-1 revealed that CINC-1 inhibited the migration of the inflammatory cells into the AC in a dose-dependent manner.It has already been reported that CINC-1, when present at concentrations over 10 ng/mL,promotes the shedding of L-selectin from the neutrophil membrane, which disables the neutrophils to interact with vascular endothelium. Thus, the high level of CINC-1 in the intravascular compartment of the LPS model seemed to be a plausible altemative to explain the lower cell migration into the AC.The LA-induced uveitis induced more inflammation in the eye than did the LPS-induced uveitis, without altering excessively the systemic homeostasis. These findings should be considered for further selection of uveitis model.