Dept of Respiratory Medicine National Heart & Lung Institute St Mary's Campus, Imperial College London, MRC and Asthma UK Centre for Allergic Mechanisms of Asthma, W2 1PG, London, UK.
Eur Respir J. 2010 Sep;36(3):646-54. doi: 10.1183/09031936.00095809. Epub 2010 Feb 11.
The majority of asthma exacerbations are caused by rhinovirus. Currently the treatment of asthma exacerbations is inadequate. Previous evidence suggests that macrolide antibiotics have anti-inflammatory and antiviral effects; however, the mechanism is unknown. We investigated the anti-rhinoviral potential of macrolides through the induction of antiviral gene mRNA and protein. Primary human bronchial epithelial cells were pre-treated with the macrolides azithromycin, erythromycin and telithromycin, and infected with minor-group rhinovirus 1B and major-group rhinovirus 16. The mRNA expression of the antiviral genes, type I interferon-β and type III interferon-λ1, interferon-λ2/3, and interferon-stimulated genes (retinoic acid inducible gene I, melanoma differentiation associated gene 5, oligoadenylate synthase, MxA and viperin) and pro-inflammatory cytokines (interleukin (IL)-6 and IL-8), and rhinovirus replication and release were measured. Azithromycin, but not erythromycin or telithromycin, significantly increased rhinovirus 1B- and rhinovirus 16-induced interferons and interferon-stimulated gene mRNA expression and protein production. Furthermore, azithromycin significantly reduced rhinovirus replication and release. Rhinovirus induced IL-6 and IL-8 protein and mRNA expression were not significantly reduced by azithromycin pre-treatment. In conclusion, the results demonstrate that azithromycin has anti-rhinoviral activity in bronchial epithelial cells and, during rhinovirus infection, increases the production of interferon-stimulated genes.
大多数哮喘恶化是由鼻病毒引起的。目前，哮喘恶化的治疗还不够充分。先前的证据表明，大环内酯类抗生素具有抗炎和抗病毒作用；然而，其机制尚不清楚。我们通过诱导抗病毒基因 mRNA 和蛋白来研究大环内酯类药物的抗鼻病毒潜力。原代人支气管上皮细胞用大环内酯类药物阿奇霉素、红霉素和泰利霉素预处理，然后用小核糖核酸病毒 1B 和大核糖核酸病毒 16 感染。测量抗病毒基因（I 型干扰素-β和 III 型干扰素-λ1、干扰素-λ2/3、干扰素刺激基因（维甲酸诱导基因 I、黑色素瘤分化相关基因 5、寡聚腺苷酸合成酶、MxA 和 viperin）和促炎细胞因子（白细胞介素（IL）-6 和 IL-8）的 mRNA 表达以及鼻病毒复制和释放。阿奇霉素，但不是红霉素或泰利霉素，显著增加了鼻病毒 1B 和鼻病毒 16 诱导的干扰素和干扰素刺激基因的 mRNA 表达和蛋白产生。此外，阿奇霉素显著降低了鼻病毒的复制和释放。鼻病毒诱导的白细胞介素（IL）-6 和 IL-8 蛋白和 mRNA 表达经阿奇霉素预处理后无明显降低。总之，结果表明阿奇霉素对支气管上皮细胞具有抗鼻病毒活性，并且在鼻病毒感染期间增加干扰素刺激基因的产生。
