中文摘要：

目的研究小剂量白细胞介素（IL）-18对早晚期Ⅱ型胶原诱导性关节炎（CIA）的作用。方法重组小鼠IL-18（0．2μgg／小鼠）每日1次腹腔注射发病前或发病晚期的CIA小鼠，连用5d，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应（RT—PCR）N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。结果小剂量IL-18早期免疫干预CIA小鼠，不能降低CIA小鼠关节炎发病率，无法延缓CIA小鼠膝关节病理学进展；滑膜和软骨附近的Th1型细胞因子和Th2型细胞因子与对照组相比差异无统计学意义。小剂量IL-18晚期免疫干预CIA小鼠，加剧了病理学进展，免疫第43天，治疗组关节炎评分（0．33±0．11）显著高于对照组（0．25±0．09）（P〈0．05）；髌骨及邻近滑膜组织的细胞因子IL-10与IL-18结合蛋白（IL-18BP）与对照组相比显著降低（P〈0．05）。结论IL-18对早期Ⅱ型胶原诱导的关节炎没有疗效。IL-18晚期免疫干预CIA小鼠，恶化了关节炎病情，其机制可能为IL-18抑制了IL-10和IL-18BP的表达。

英文摘要：

Objective To investigate the effect of exogenous murine interlukin- 18 （mIL- 18 ） on early and established murine collagen-induced arthritis （CIA）. Methods Mice were injected intraperitoneally with IL-18 （0.2 μg/mouse） daily for 5 days before or after the onset of CIA. The response was monitored visu- ally by macroscopic scoring. Reverse transcription-polymerase chain reaction （RT-PCR） was employed to determine the mRNA expression of cytokines in patella with adjacent synovium in CIA mouse. Histology of knee synovium was used to assess the occurrence of cartilage destruction and bone erosions. Results IL-18 alone had no effect on macroscopic score, occurrence of arthritis, advancement of histology on early stage of CIA. Moreover, expression of Th1 cytokines and Th2 cytokines in the synovial tissue and articular cartilage remained unchanged compared with the control group, however, a pronounced progression of histology was found in mice treated with IL-18 in established CIA. Forty-three days after immunization, the macroscopic score in the treated group （0.33±0.11） was significantly improved than in the control group （0.25±0.09） （P〈 0.05）. Moreover, the mRNA levels of IL-10 and IL-18BP both in the synovial tissue and in the articular cartilage in the treated groups decreased significantly than those in the control groups （P〈0.05）. Conclusion Low dose mIL-18 alone has no effect on early stage CIA. But pronounced exacerbation is found in mice treated with IL-18 on established arthritis, which supports that IL-18 initiates this effect by inhibiting IL-10 and IL-18 BP.