类风湿关节炎滑膜白细胞介素18的表达

The expression of interleakin-18 in synovium from patients with rheumtoid arthritis

目的:探讨类风湿关节炎(RA)滑膜IL-18表达及其与Th1/Th2平衡和疾病活动的关系;方法:以特征性细胞因子IFN-7、IL-4作为Th1、Th2亚群的代表性指标,用半定量RT-PCR方法测定RA、OA患者及正常人滑膜组织中IL-18、IL-4、IFN-γmRNA水平。并观察IL-18mRNA与IL-4、IFN-γ及疾病活动性的关系,同时以免疫组化及原位杂交技术从形态学方面观察RA滑膜中IL-18的分布。结累:1.RA滑膜IL-18mRNA水平显著高于OA及正常滑膜(3.533±0.985vs 0.973±0.195 and 3.533±0.985vs0.050±0.087 P均小于0.01)。2.相关分析显示:RA滑膜IL18mRNA与IFN-γ、ESR显著正相关。3.滑膜原位杂交也显示,所有RA滑膜均呈现较强的阳性反应。而11例OA患者仅两例出现弱的阳性染色,正常滑膜没有阳性信号。4.免疫组化染色显示RA滑膜IL-18不仅阳性率,而且其染色反应的强度也明显超过OA滑膜与正常对照。RA患者滑膜IL-18阳性信号分布于成纤维细胞及其周围的间隙中。

Objective: Interleukin-18, originally termed as an IFN-Υ-inducing factor, is a novel pro-inflammatory cytokine which may polarize T cells toward Thl cell function. This study was designed to research the expression of IL-18 at the sites of rheumatoid inflammation, to understand the relationship exists between the expression of IL-18 and the ratio of Thl/Th2 in RA, to learn the correlationship between IL-18 level and activity of the disease. Methods:31 case of synovial samples from 15 cases of patients with RA , and 11 cases of patients with OA and 5 normal controls were detected. All RA patients matched the standard the of ARA 1987. The expression of IFN-Υ, IL-4, and IL-18 mRNA were determined by semi-quantitive RT-PCR. The immuno-histochemical staining by using cytokine-specific IL-18 antibody and in-situ-hybridization by using IL-18 cDNA probe was conducted to detected the expression of IL-18 in the synovial tissue from RA, OA, and normal subjects. Results: 1). Synovial tissues from RA patients were found to contain greater levels of IL-18 mRNA than that from OA and controls(3. 533 ± 0. 985vs 0. 973 ± 0.195 and 3.533±0.985vs0.050±0.087 P<0.01, respectively); 2).Positive immuno-histochemical staining by IL-18 antibody and hybridization in situ by IL-18 cDNA probe was found in all RA synovial tissues, partly in OA synovial tissues, no normal controls showed positive stainning, the both positive ratio in RA subjects were higher than that in OA group and normal controls(P<0.01); 3). IL-18 mRNA levels were correlated with IFN-ΥmRNA ( relative coefficients r=0.598, pvalue less than 0.05) and with the disease activity as assessed by levels of erythrocyte sedimentation rate(r=0.485, p<0.05). Conclusion: IL-18 is produced abundantly in the joints of RA, and play an important role in the pathogenesis of RA by stimulating the IFN-Υ-dominated Thl response, and may be related to activities of the disease .