Respiratory syncytial virus infection results in airway hyperresponsiveness and enhanced airway sensitization to allergen
Respiratory syncytial virus infection results in airway hyperresponsiveness and enhanced airway sensitization to allergen
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DOI：
10.1172/jci119516
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发表时间：
1997-07-01
影响因子：
15.9
通讯作者：
Gelfand, EW
中科院分区：
文献类型：
--
作者：
Schwarze, J;Hamelmann, E;Gelfand, EW
病毒性呼吸道感染可通过目前尚未确定的机制诱发哮喘的发生。使用呼吸道合胞病毒（RSV）感染的小鼠模型，急性感染与气道高反应性以及随后对变应原致敏的增强反应相关。我们证明，急性病毒感染导致气道对吸入乙酰甲胆碱的反应性增加以及肺嗜酸性粒细胞和嗜酸性粒细胞炎症，这种应答与体外支气管周围淋巴结细胞中Th-1型细胞因子的主要产生有关，RSV感染后通过气道对卵清蛋白致敏的小鼠出现气道对乙酰甲胆碱的反应性增加以及肺嗜酸性粒细胞和嗜酸性粒细胞炎症，与Th-2型细胞因子的主要产生相关。用抗IL-5抗体治疗小鼠，可以消除急性感染小鼠和感染后致敏小鼠的气道高反应性和嗜酸性粒细胞炎症，但不能消除中性粒细胞炎症。我们得出的结论是，RSV感染导致急性期气道高反应性，并导致免疫功能的变化，可以增强感染后气道对抗原致敏的作用，在这两种情况下，气道高反应性与肺嗜酸性粒细胞性炎症密切相关，该模型为进一步分析病毒性呼吸道感染对气道敏感性的影响和气道反应性改变的发展提供了一种手段。
Viral respiratory infections can predispose to the development of asthma by mechanisms that are presently undetermined. Using a murine model of respiratory syncytial virus (RSV) infection, acute infection is associated with airway hyperresponsiveness as well as enhanced responses to subsequent sensitization to allergen, We demonstrate that acute viral infection results in increased airway responsiveness to inhaled methacholine and pulmonary neutrophilic and eosinophilic inflammation, This response is associated with predominant production of Th-l-type cytokines in peribronchial lymph node cells in vitro, Mice sensitized to ovalbumin via the airways after RSV infection developed increased airway responsiveness to methacholine and pulmonary eosinophilic and neutrophilic inflammation, associated with the predominant production of Th-2-type cytokines. Treatment of the mice with anti-IL-5 antibody abolished ah-way hyperresponsiveness and eosinophilic but not neutrophilic inflammation in both acutely infected mice and mice sensitized after infection, We conclude that RSV infection results in airway hyperresponsiveness in the acute phase and leads to changes in immune function that can enhance the effects of airway sensitization to antigen after infection, Ln both situations, airway hyperresponsiveness is closely associated with pulmonary eosinophilic inflammation, This model provides a means for further analyzing the influence of viral respiratory infections on airway sensitization and the development of altered airway responsiveness.