类风湿关节炎患者血清滑液和滑膜组织白细胞介素-18的水平及意义

Expression of interleukin-18 in serum,synovial fluid and synovial tissue in patients with rheumatoid arthritis

目的 研究类风湿关节炎 (RA)患者血清、滑液中白细胞介素 18(IL 18)蛋白及滑膜组织IL 18mRNA表达水平 ,探讨其在RA致病中的作用。方法 应用双抗夹心酶联免疫吸附(ELISA)法和细胞生物法分别测定RA患者血清、滑液中IL 18蛋白水平和生物活性 ,同时还检测NO、前列腺素E2 的含量 ;采用半定量RT PCR法检测滑膜组织IL 18mRNA表达水平。以骨关节炎(OA)病人及因外伤截肢的正常人作对照。结果 RA患者血清、滑液中IL 18蛋白水平和生物活性均显著高于对照组 ,滑液中量及活性比血清高 ;RA滑膜组织IL 18mRNA表达水平也明显高于对照组。结论 过度表达的IL 18参与了RA的致病过程 ;选择性地抑制IL 18生物活性 ,将是RA治疗的新途径。

Objective To investigate the expression of interleukin 18 (IL 18) in serum,synovial fluid and synovial tissue of patients with rheumatoid arthritis (RA) and to identify its pathological role in RA.Methods The serum,synovial fluid and synovial tissue were obtained from patients with RA,and samples from patients with osteoarthritis (OA) and from healthy human were used as control groups.Levels of IL 18 protein in serum and synovial fluid were measured by enzyme linked immunosorbent assay (ELISA).Expression of IL 18 mRNA in synovial tissus was determined by semi quantitative reverse transcriptase polymerase chain reaction (RT PCR).The biologic activity of IL 18 in serum and synovial fluid was detected on the basis of IFN γ secretion from IL 18 responding human myelomonocytic KG 1 cells.Expression of iNOS and COX 2 mRNA in synovial tissue was also determined,and productions of NO and PGE 2 in serum and synovial fluid were measured by enzyme reduction method and ELISA.Results Levels of IL 18 protein and biologic activity of IL 18 in both serum and synovial fluid of patients with RA were significantly increased compared with corresponding samples of the two control groups.In addition,the expression of IL 18 mRNA in synovial tissue of patients with RA was also significantly increased compared with samples of the two control groups.Conclusion The over expressed IL 18 may play an important role in the pathogenesis of RA.