Division of Paediatric Respiratory Medicine, University Children's Hospital, Berne, Switzerland Dept of Clinical Research, University of Berne, Berne, Switzerland Graduate School for Cellular and Biomedical Sciences, University of Berne, Berne, Switzerland.
Division of Paediatric Respiratory Medicine, University Children's Hospital, Berne, Switzerland Dept of Clinical Research, University of Berne, Berne, Switzerland.
Eur Respir J. 2015 Feb;45(2):428-39. doi: 10.1183/09031936.00102014. Epub 2014 Oct 30.
Virus-associated pulmonary exacerbations, often associated with rhinoviruses (RVs), contribute to cystic fibrosis (CF) morbidity. Currently, there are only a few therapeutic options to treat virus-induced CF pulmonary exacerbations. The macrolide antibiotic azithromycin has antiviral properties in human bronchial epithelial cells. We investigated the potential of azithromycin to induce antiviral mechanisms in CF bronchial epithelial cells. Primary bronchial epithelial cells from CF and control children were infected with RV after azithromycin pre-treatment. Viral RNA, interferon (IFN), IFN-stimulated gene and pattern recognition receptor expression were measured by real-time quantitative PCR. Live virus shedding was assessed by assaying the 50% tissue culture infective dose. Pro-inflammatory cytokine and IFN-β production were evaluated by ELISA. Cell death was investigated by flow cytometry. RV replication was increased in CF compared with control cells. Azithromycin reduced RV replication seven-fold in CF cells without inducing cell death. Furthermore, azithromycin increased RV-induced pattern recognition receptor, IFN and IFN-stimulated gene mRNA levels. While stimulating antiviral responses, azithromycin did not prevent virus-induced pro-inflammatory responses. Azithromycin pre-treatment reduces RV replication in CF bronchial epithelial cells, possibly through the amplification of the antiviral response mediated by the IFN pathway. Clinical studies are needed to elucidate the potential of azithromycin in the management and prevention of RV-induced CF pulmonary exacerbations.
病毒相关性肺部恶化，常与鼻病毒（RV）相关，导致囊性纤维化（CF）发病。目前，仅有少数治疗方法可用于治疗病毒引起的 CF 肺部恶化。大环内酯类抗生素阿奇霉素在人支气管上皮细胞中具有抗病毒特性。我们研究了阿奇霉素诱导 CF 支气管上皮细胞抗病毒机制的潜力。CF 和对照儿童的原代支气管上皮细胞在用阿奇霉素预处理后感染 RV。通过实时定量 PCR 测量病毒 RNA、干扰素（IFN）、IFN 刺激基因和模式识别受体表达。通过测定 50%组织培养感染剂量来评估活病毒脱落。通过 ELISA 评估促炎细胞因子和 IFN-β的产生。通过流式细胞术研究细胞死亡。与对照细胞相比，CF 中的 RV 复制增加。阿奇霉素在不诱导细胞死亡的情况下使 CF 细胞中的 RV 复制减少了七倍。此外，阿奇霉素增加了 RV 诱导的模式识别受体、IFN 和 IFN 刺激基因 mRNA 水平。虽然刺激抗病毒反应，但阿奇霉素不能预防病毒引起的促炎反应。阿奇霉素预处理可减少 CF 支气管上皮细胞中的 RV 复制，可能通过 IFN 途径介导的抗病毒反应放大。需要进行临床研究以阐明阿奇霉素在管理和预防 RV 引起的 CF 肺部恶化中的潜力。
