The Involvement of Glucocorticoids in Psychological Stress-Induced Exacerbations of Experimental Allergic Asthma
The Involvement of Glucocorticoids in Psychological Stress-Induced Exacerbations of Experimental Allergic Asthma
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DOI：
10.1159/000360577
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发表时间：
2014-01-01
影响因子：
2.8
通讯作者：
Ohno, Isao
中科院分区：
文献类型：
--
作者：
Okuyama, Kaori;Dobashi, Kazuhisa;Ohno, Isao
背景：心理应激与哮喘症状的加重有关。糖皮质激素(GC)是一种在应激状态下释放的应激激素，通过激发抗原提呈细胞产生较低水平的IL-12以及减少调节性T细胞的发育，有可能使免疫反应转向以Th2为主的反应。然而，GC在心理应激诱导的过敏性哮喘加重中的作用尚未阐明。方法：致敏小鼠暴露于束缚应激和强迫游泳应激，期间给予GC受体拮抗剂或GC合成抑制剂，然后吸入抗原。对应激和非应激小鼠的血液皮质酮水平进行了测量。吸入抗原后，观察雾化吸入乙酰甲胆碱后的气道反应、上皮性黏液分泌和气道炎症反应，并测定支气管肺泡灌洗液中IL-13的含量。结果：应激可显著提高皮质酮水平。应激小鼠的过敏性呼吸道反应和吸入抗原引起的IL-13含量升高明显高于非应激小鼠。应激暴露期间给予GC受体拮抗剂和GC合成抑制剂可显著减轻抗原攻击应激小鼠呼吸道反应的加重和IL-13含量的增加。结论：这些结果表明，应激时GC释放的增加对暴露后过敏性呼吸道反应的加重具有启动作用，提示神经内分泌轴在心理应激与哮喘加重之间起着病理生理学作用。(C)2014年S.Karger AG，巴塞尔
Background: Psychological stress is associated with the aggravation of asthma symptoms. Glucocorticoids (GC), which are stress hormones released upon exposure to stress, have the potential to shift immune responses towards a predominant Th2 response by priming antigen-presenting cells to produce lower levels of IL-12 as well as reducing the development of regulatory T cells. However, the involvement of GC in psychological stress-induced exacerbations of allergic asthma has not yet been clarified. Methods: Sensitized mice were exposed to restraint stress followed by forced swimming stress, during which a GC receptor antagonist or a GC synthesis inhibitor was administered, and then antigen was inhaled. Corticosterone levels in the blood were measured in stressed and nonstressed mice. After antigen inhalation, the airway responses to aerosolized methacholine, epithelial mucus secretion and airway inflammation were evaluated, and the IL-13 contents in bronchoalveolar lavage fluid were measured. Results: The exposure to stress significantly increased corticosterone levels. Allergic airway responses and the increase of IL-13 contents evoked by antigen inhalation were significantly higher in stressed mice than in non-stressed mice. The administration of a GC receptor antagonist and a GC synthesis inhibitor during stress exposure significantly reduced the exacerbation of the airway responses and the increase of IL-13 contents in stressed mice challenged with antigen. Conclusions: These results indicate that the increased release of GC upon exposure to stress has a priming effect on the aggravation of allergic airway responses following the exposure, suggesting a pathophysiological role for the neuroendocrine axis in linking psychological stress to asthma exacerbations. (C) 2014 S. Karger AG, Basel