Background. Obliterative bronchiolitis (OB) was a main cause of deterioration of long-term prognosis in lung transplant recipients after the first posttransplant year. Proinflammatory cytokine interleukin-18 (IL-18) strengthened both the natural immunity and acquired immunity and played an important role in organ transplantation. The roles of IL-18 in the occurrence, development, and drug treatment of OB remained unclear. Methods. Small interfering RNA (siRNA) against mouse IL-18 (siRNA-IL-18) was used to silence IL-18 expression. Mouse heterotopic tracheal transplantation model was used to simulate OB. Recipient mice were divided into 5 groups () according to donor mouse strains and drug treatment: isograft group, allograft group, allograft+tacrolimus group, allograft+azithromycin group, and allograft+tacrolimus+azithromycin group. The luminal obliteration rates were pathological evaluation. Expressions of cytokines and MMPs were detected by real-time PCR, western blot, and enzyme chain immunosorbent assay (ELISA). Results. The luminal obliteration rates of IL-18 of the siRNA-IL-18 group were significantly lower than those of the negative control group () and the blank control group (). mRNA expressions of IFN-γ, EMMPRIN, MMP-8, and MMP-9 of the siRNA-IL-18 group were significantly lower than those of the negative and blank control groups. No tracheal occlusion occurred in grafts of the isograft group. The rates of tracheal occlusion of the allograft group, allograft+tacrolimus group, allograft+azithromycin group, and allograft+tacrolimus+azithromycin group were %, %, %, and %, respectively. There were significant differences between the 4 groups (). Serum protein expressions of IL-17 (), IL-18 (), IFN-γ (), and MMP-9 () were significantly decreased in the allograft+tacrolimus+azithromycin group compared to the allograft group. Conclusions. IL-18 could be a novel molecular involved in the occurrence, development, and drug treatment of OB.

中文翻译：

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Interleukin-18：肺移植后闭塞性细支气管炎的发生、发展和药物治疗的新参与者

背景。闭塞性细支气管炎 (OB) 是移植后第一年肺移植受者长期预后恶化的主要原因。促炎细胞因子白细胞介素18（IL-18）增强了自然免疫和获得性免疫，在器官移植中发挥了重要作用。IL-18 在 OB 的发生、发展和药物治疗中的作用尚不清楚。方法。针对小鼠 IL-18 (siRNA-IL-18) 的小干扰 RNA (siRNA) 用于沉默 IL-18 表达。小鼠异位气管移植模型用于模拟OB。受体小鼠被分为5组（)根据供体小鼠品系和药物处理：同种移植组、同种异体移植组、同种移植+他克莫司组、同种移植+阿奇霉素组、同种移植+他克莫司+阿奇霉素组。管腔闭塞率是病理评估。通过实时PCR、蛋白质印迹和酶链免疫吸附试验(ELISA)检测细胞因子和MMPs的表达。结果。siRNA-IL-18组的IL-18腔闭塞率显着低于阴性对照组（)和空白对照组 (）。siRNA-IL-18组IFN- γ、EMMPRIN、MMP-8、MMP-9的mRNA表达显着低于阴性和空白对照组。同种移植物组未发生气管阻塞。同种异体组、同种异体+他克莫司组、同种异体+阿奇霉素组、同种异体+他克莫司+阿奇霉素组气管闭塞率分别为%, %, ％， 和 ％， 分别。4组间有显着差异（）。IL-17的血清蛋白表达（), IL-18 (),干扰素-γ ()和 MMP-9 ()与同种异体移植组相比，同种异体移植+他克莫司+阿奇霉素组显着降低。结论。IL-18 可能是参与 OB 发生、发展和药物治疗的新型分子。