Brandt Eric B, Scribner Troy A, Akei Hiroko Saito, Rothenberg Marc E
Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
J Allergy Clin Immunol. 2006 Aug;118(2):420-7. doi: 10.1016/j.jaci.2006.06.009.
Gastrointestinal allergy often precedes or coexists with respiratory allergy.
We hypothesized that established experimental gastrointestinal allergy would prime for the development of allergic respiratory responses.
BALB/c mice were sensitized with ovalbumin (OVA) in the presence of aluminum potassium sulfate and then subjected to intragastric saline or OVA challenges. After the development of allergen-induced gastrointestinal allergy, mice were intranasally exposed to either saline, OVA, or a neoaeroallergen house dust mite (HDM) extract. Airway inflammation (eg, bronchoalveolar lavage fluid cellularity, cytokine levels, and OVA-specific antibody levels) and airway responsiveness to methacholine exposure were assessed after intranasal allergen exposure.
A single intranasal exposure to OVA induced significantly more airway inflammation in intragastric OVA-challenged mice compared with that seen in intragastric saline-treated mice. Kinetic analysis revealed that the observed amplification of lung inflammation was sustained for up to 12 days after the last intragastric OVA challenge after resolution of blood eosinophilia. When mice with gastrointestinal allergy were repeatedly challenged with HDM in the respiratory tract, they experienced enhanced airway inflammation, including bronchoalveolar lavage fluid eosinophilia and increased IL-13 levels.
Taken together, our results demonstrate that OVA-induced gastrointestinal allergy enhances not only allergic airway responses to OVA but also to HDM, an unrelated aeroallergen.
Experimental gastrointestinal allergy primes for responses to allergens in the respiratory tract, enhancing antigen-specific antibody and T(H)2 cytokine production, airway inflammation, and airway hyperresponsiveness.
胃肠道过敏常先于呼吸道过敏出现或与之并存。
我们假设已确立的实验性胃肠道过敏会引发过敏性呼吸道反应的发生。
将BALB/c小鼠在硫酸铝钾存在的情况下用卵清蛋白（OVA）致敏，然后进行胃内生理盐水或OVA激发。在变应原诱导的胃肠道过敏形成后，将小鼠经鼻暴露于生理盐水、OVA或一种新的气源性变应原屋尘螨（HDM）提取物。在经鼻变应原暴露后评估气道炎症（如支气管肺泡灌洗液体细胞成分、细胞因子水平和OVA特异性抗体水平）以及气道对乙酰甲胆碱暴露的反应性。
与胃内给予生理盐水处理的小鼠相比，单次经鼻暴露于OVA在胃内给予OVA激发的小鼠中诱导出显著更多的气道炎症。动力学分析显示，在血液嗜酸性粒细胞增多消退后，在最后一次胃内OVA激发后长达12天观察到的肺部炎症放大持续存在。当患有胃肠道过敏的小鼠在呼吸道中反复接受HDM激发时，它们经历了增强的气道炎症，包括支气管肺泡灌洗液体嗜酸性粒细胞增多和IL-13水平升高。
综上所述，我们的结果表明OVA诱导的胃肠道过敏不仅增强了对OVA的过敏性气道反应，而且增强了对一种不相关的气源性变应原HDM的反应。
实验性胃肠道过敏引发对呼吸道中变应原的反应，增强抗原特异性抗体和辅助性T细胞2（Th2）细胞因子产生、气道炎症和气道高反应性。
