Double-stranded RNA evokes exacerbation in a mouse model of corticosteroid refractory asthma
Double-stranded RNA evokes exacerbation in a mouse model of corticosteroid refractory asthma
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DOI：
10.1042/cs20150292
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发表时间：
2015-12-01
期刊：
影响因子：
6
通讯作者：
Miralpeix, Montserrat
中科院分区：
文献类型：
--
作者：
De Alba, Jorge;Otal, Raquel;Miralpeix, Montserrat
RNA病毒是呼吸道感染的主要原因，并且已知会加剧哮喘和其他呼吸道疾病。我们的目的是测试poly（I：C）（聚肌苷酸：聚胞苷酸）（一种病毒替代物）在FCA（弗氏完全佐剂）中引起HDM（屋尘螨）驱动的严重哮喘模型中加重的能力。在FCA-HDM致敏动物中，在HDM激发周围鼻内给予Poly（I：C）。在激发后不同时间点评价AHR（气道高反应性）、BALF（支气管肺泡灌洗液）炎性浸润、HDM特异性免疫球蛋白和细胞因子/趋化因子释放的变化。还评估了口服地塞米松的效果。当在HDM激发前24小时给予聚（I：C）时，病情加重，其特征在于AHR增强和BALF中中性粒细胞、巨噬细胞和淋巴细胞数量增加。Th 1、Th 2和Th 17细胞因子在攻击后不同时间点也升高。肺组织中的支气管周围和肺泡炎症也增加。AHR和炎症浸润显示对地塞米松治疗的敏感性降低。我们已经建立了一个模型，模拟病毒加重的关键方面，在皮质类固醇难治性哮喘表型，可用于评估这种情况下的新疗法。
RNA viruses are a major cause of respiratory infections and are known to exacerbate asthma and other respiratory diseases. Our aim was to test the ability of poly(I:C) (polyinosinic: polycytidylic acid), a viral surrogate, to elicit exacerbation in a model of severe asthma driven by HDM (house dust mite) in FCA (Freund's complete adjuvant). Poly(I:C) was administered intranasally around the HDM challenge in FCA-HDM-sensitized animals. Changes in AHR (airway hyperresponsiveness), BALF (bronchoalveolar lavage fluid) inflammatory infiltrate, HDM-specific immunoglobulins and cytokine/chemokine release were evaluated at different points after the challenge. The effect of oral dexamethasone was also assessed. Exacerbation was achieved when poly(I:C) was administered 24 h before the HDM challenge and was characterized by enhanced AHR and an increase in the numbers of neutrophils, macrophages and lymphocytes in the BALF. Th1, Th2 and Th17 cytokines were also elevated at different time points after the challenge. Peribronchial and alveolar inflammation in lung tissue were also augmented. AHR and inflammatory infiltration showed reduced sensitivity to dexamethasone treatment. We have set up a model that mimics key aspects of viral exacerbation in a corticosteroid-refractory asthmatic phenotype which could be used to evaluate new therapies for this condition.