Remund Kaspar, Rechsteiner Thomas, Rentsch Katharina, Vogt Peter, Russi Erich W, Boehler Annette
Division of Pulmonary Medicine, University Hospital Zurich, Zurich, Switzerland.
Transplantation. 2008 Mar 15;85(5):726-31. doi: 10.1097/TP.0b013e31816632ed.
Ciprofloxacin is widely used to treat respiratory tract infections. Like other fluoroquinolones, ciprofloxacin has immunomodulatory effects; however, it is unknown whether these effects are beneficial in the setting of lung transplantation. We investigated potential immunomodulatory effects of ciprofloxacin in a model of posttransplant bronchiolitis obliterans.
The heterotopic tracheal transplantation model in rats was used. Three groups received ciprofloxacin and underwent different immunosuppressive regimens of cyclosporine A, that is, no immunosuppression, insufficient immunosuppression, or low-dose immunosuppression. Three groups underwent the same immunosuppressive regimen but had no ciprofloxacin treatment. Tracheas were harvested after 21 days and examined with respect to histology and expression of selected cytokines.
The allografts of animals treated with ciprofloxacin showed less airway obliteration compared with allografts of untreated animals. When combined with low-dose immunosuppression ciprofloxacin showed beneficial effects in preventing airway obliteration and rejection of the respiratory epithelium. Cytokine gene expression of the allografts treated with ciprofloxacin was higher with respect to transforming growth factor-beta and equal with respect to tumor necrosis factor-alpha and interferon-gamma compared with controls. When applied in combination with cyclosporine A, ciprofloxacin lowered the expression of transforming growth factor-beta and tumor necrosis factor-alpha and increased interferon-gamma expression.
Ciprofloxacin attenuates airway rejection after tracheal transplantation. Genetic expression of mediators that are known to play an important role in mediating rejection in this model supports an immunomodulatory and antifibrotic role of ciprofloxacin. These findings suggest that further clinical studies are needed to investigate whether ciprofloxacin in addition to its bactericidal effect might be beneficial in the treatment of human posttransplant bronchiolitis obliterans.
环丙沙星广泛用于治疗呼吸道感染。与其他氟喹诺酮类药物一样，环丙沙星具有免疫调节作用；然而，这些作用在肺移植环境中是否有益尚不清楚。我们在移植后闭塞性细支气管炎模型中研究了环丙沙星的潜在免疫调节作用。
采用大鼠异位气管移植模型。三组接受环丙沙星治疗，并接受不同的环孢素A免疫抑制方案，即无免疫抑制、免疫抑制不足或低剂量免疫抑制。三组接受相同的免疫抑制方案，但未接受环丙沙星治疗。21天后取出气管，进行组织学检查和所选细胞因子表达检测。
与未治疗动物的同种异体移植物相比，接受环丙沙星治疗的动物的同种异体移植物气道闭塞较少。当与低剂量免疫抑制联合使用时，环丙沙星在预防气道闭塞和呼吸道上皮排斥方面显示出有益作用。与对照组相比，接受环丙沙星治疗的同种异体移植物中转化生长因子-β的细胞因子基因表达较高，肿瘤坏死因子-α和干扰素-γ的表达相同。当与环孢素A联合应用时，环丙沙星降低了转化生长因子-β和肿瘤坏死因子-α的表达，并增加了干扰素-γ的表达。
环丙沙星可减轻气管移植后的气道排斥反应。已知在该模型中介导排斥反应中起重要作用的介质的基因表达支持环丙沙星的免疫调节和抗纤维化作用。这些发现表明，需要进一步的临床研究来调查环丙沙星除杀菌作用外，是否对治疗人类移植后闭塞性细支气管炎有益。
