Stress enhances airway reactivity and airway inflammation in an animal model of allergic bronchial asthma
Stress enhances airway reactivity and airway inflammation in an animal model of allergic bronchial asthma
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DOI：
10.1097/01.psy.0000088582.50468.a3
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发表时间：
2003-09-01
影响因子：
3.3
通讯作者：
Klapp, BF
中科院分区：
文献类型：
--
作者：
Joachim, RA;Quarcoo, D;Klapp, BF
目的：尽管长期以来临床假设压力和哮喘发病率是相关的，但关于机制的令人信服的实验证据一直不可用。已知广泛的免疫学、内分泌学和神经元途径介导和调节全身性应激反应。有趣的是，这些介质中的大多数在启动和维持支气管哮喘相关症状中起着至关重要的作用。为了探索应激与哮喘恶化之间的潜在机制，我们建立了一种结合过敏性气道炎症和应激的动物模型。方法：卵白蛋白（OVA）腹腔注射致敏CBA/J小鼠，经气道雾化吸入激发。此外，一些小鼠通过暴露于超声应激源而受到应激。用电场刺激离体气管平滑肌测定气道高反应性。获得支气管肺泡灌洗液（BAL）并测定细胞数量。通过ELISA测定BAL中IL-4、IL-5和IFN-γ的细胞因子水平。结果：我们的研究结果表明，外源性压力显着提高了OVA致敏和激发小鼠的气道反应性。此外，应激可显著增加过敏原诱导的气道炎症，表现为支气管肺泡灌洗液中白细胞（即嗜酸性粒细胞）数量增加。结论：我们在过敏性支气管哮喘的动物模型中发现了进一步的证据，表明应激确实可以加剧气道高反应性和气道炎症，现在引入一种新的小鼠模型来识别应激触发的通路，包括神经激素，神经肽和炎症标记物等介质。
Objective: Despite the long-standing clinical assumption that stress and asthma morbidity are associated, convincing experimental evidence on mechanisms has been unavailable. A wide range of immunological, endocrinological, and neuronal pathways are known to mediate and modulate a systemic stress response. Interestingly, most of these mediators play a crucial role in initiating and perpetuating symptoms associated with bronchial asthma. To explore potential mechanisms linking stress to asthma exacerbation we developed an animal model that combines allergic airway inflammation and exposure to stress. Methods: CBA/J mice were sensitized by intraperitoneal injection of ovalbumin (OVA) and challenged with OVA aerosol via the airways. Additionally, some mice were stressed by exposure to an ultrasonic stressor. Airway hyperreactivity (AHR) was measured in vitro by electric field stimulation (EFS) of tracheal smooth muscle elements. Bronchoalveolar lavage fluid (BAL) was obtained and cell numbers determined. Cytokine levels of IL-4, IL-5, and IFN-gamma in BAL were determined by ELISA. Results: Our findings demonstrate that exogenously applied stress dramatically enhances airway reactivity in OVA-sensitized and challenged mice. Further, stress significantly increases allergen-induced airway inflammation identified by increased leukocyte (ie, eosinophil) numbers in bronchoalveolar lavage fluids. Conclusions: We found further evidence that stress can indeed exacerbate airway hyperreactivity and airway inflammation in an animal model of allergic bronchial asthma and now introduce a novel murine model to identify stress-triggered pathways, including mediators as neurohormones, neuropeptides, and markers of inflammation.