小剂量白细胞介素-18联合白细胞介素-10在早期Ⅱ型胶原诱导性关节炎中的作用研究  

Study to low-dose interleukin-18 combined with interlukin-10 in early stage of mouse collagen

作　　者：代巧妹[1] 张凤山[1] 李洋[1] 

机构地区：[1]哈尔滨医科大学附属二院风湿科,150086

出　　处：《中华风湿病学杂志》2010年第6期388-390,441,共4页Chinese Journal of Rheumatology

基　　金：国家自然科学基金（30600561）;国家自然科学基金面上项目（30972739）;黑龙江省科学技术厅青年专项（QC06C051）;黑龙江省人事厅留学回国人员择优资助项目（2007-44）

摘　　要：目的 研究不同细胞因子微环境下,白细胞介素（IL）-18对早期Ⅱ型胶原诱导性关节炎（CIA）的作用.方法 CIA小鼠,发病前给予每只重组小鼠腹腔注射IL-18（0.2 μg/d）/IL-10（0.1 μg/d）,IL-18（0.2 μg/d）IL-4（0.1 μg/d）,IL-18（0.2 μg/d）IL-12（0.1 μg/d）,连用5 d,用关节炎评分评估关节炎病情的进展,用反转录聚合酶链反虚（RT-PCR）测定CIA小鼠髌骨及邻近滑膜组织的细胞因子表达水平;用组织学染色评价膝关节的软骨和骨破坏.采用Wilcoxon rank检验. 结果 IL-18/IL-4组关节炎评分轻度降低.IL-18/IL-10联合治疗有效抑制了C1A小鼠的关节炎症反应,免疫第38天治疗组关节炎评分（0.12±0.20）显著低于对照组（0.29±0.19,P〈0.05）,阻止了滑膜部位的炎细胞浸润,防止了软骨的破坏.滑膜和其附近软骨的Th1型细胞因子[IL-18（0.22±0.06）,IL-12（0.14±0.05）]与炎症性细胞因子[IL-6（0.22±0.11）]水平与对照组相比显著降低（P〈0.05）,Th2型细胞因子[IL-10（6.35±0.12）,IL-4（3.57±0.13）]水平与对照组相比明显升高（P〈05）. IL-18R（0.40±0.15）水平明显降低（P〈0.05）.T-bet水平降低,转录因子（GATA）-3水平（5.7l±0.11）显著升高（P〈0.05）.结论 IL-18/IL-10免疫干预尚未发病的CIA小鼠,可以抑制Th1型免疫反应,使免疫反应向Th2逆转,其机制可能为下调了IL-18/IL-18R水平,诱导了转录因子GATA-3的表达.Objective To investigate the effect of exogenous murine interleukin-18 （IL-18） on early mouse collagen II-induced arthritis （CIA）. Methods Mice were injected intraperitoneallg IL-18 （0.2 ug/d） combination with IL-10 （0.1 ug/d）, IL-4 （0.1 ug/d） and IL-12 （0.1ug/d） daily for five days before the onset of CIA. The arthritis response was monitored visually by macroscopic scoring. Reverse transcription- polymerase chain reaction （RT-PCR） was employed to determine the mRNA expression of cytokine in patella with adjacent synovium in CIA mouse. Histology of knee was examined to assess the occurrence of cartilage destruction and bone erosion. Wilcoxon rank test was selected. Results IL-18/IL-4 treatment could slightly suppress the macroscopic score of arthritis, but a more pronounced amelioration was found in mice treated with the combination of IL-18 and IL-10 during early treatment. On 38 days after immunizatian macroscopic score in treated group （0.12±0.20） was significantly improves than in the control group （0.29±0.19, P〈0.05）. This resulted in both the suppression of macroscopic signs of imflammation and the reduction of cellular infiltrates in the synovial tissue, which provided the protection against cartilage destruction. Moreover, the expression of Thl cytokines [IL-18 （0.22±0.06）, IL-12 （0.14±0.05）1 and inflammatory cytokine [IL-6 （0.22±0.11）] was greatly inhibited both in the synovial tissue and in the articular cartilage in the treatment groups compared with those in the control groups（P〈0.05）. However, the mRNA levels of Th2 cytokines [IL-10 （6.35±0.12）, IL-4 （ 3.57±0.13 ） ] were up-regulated after IL- 18/IL- 10 treatment （ P〈0.05 ）. Moreover, IL- 18R （ 0.40±0.15 ） levels were down-regulated compared with those in the control group （P〈0.05）. T-bet mRNA levels were decreased in IL-18/IL-10 compared with the control group, and GATA-3 mRN A （5.71±0.11 ） levels were significantly higher than those in the control group �

关 键 词：白细胞介素18 白细胞介素10 关节炎 实验性 

分 类 号：R285.5[医药卫生—中药学]