GlaxoSmithKline Research Centre Zagreb Limited, Zagreb, Croatia.
Inflamm Res. 2009 Nov;58(11):773-81. doi: 10.1007/s00011-009-0046-2. Epub 2009 May 8.
To investigate whether challenge with increasing allergen doses could differently affect allergen-induced airway hyperresponsiveness (AHR) and inflammatory cell accumulation in mouse model of asthma, providing an experimental model to investigate their relationship.
AHR and accumulation of inflammatory cells in bronchoalveolar lavage fluid (BALF) and into the lungs were compared in ovalbumin-sensitized mice that were challenged intranasally with 2.5, 10, 25 or 100 microg of ovalbumin/mouse.
Both AHR and inflammatory cell accumulation were proportional to the ovalbumin dose used for challenge. However, in group challenged with 10 microg of ovalbumin airway inflammation was present, although allergen-induced AHR was not detected. Additional analysis indicated that neither mucous hyperproduction nor eosinophil degranulation could be correlated to presence of AHR in this model, whereas concentration of interleukin (IL)-13 in BALF was increased only in those groups in which AHR was present.
Altogether, intranasal challenge of mice with increasing allergen doses could serve as a suitable experimental system for investigation of mechanisms by which airway inflammation leads to allergen-induced AHR. Our initial findings are in line with previous reports that dissociate AHR from amount of eosinophil accumulation and imply the role of IL-13 in this process.
研究递增过敏原剂量激发是否能影响哮喘小鼠模型中过敏原诱导的气道高反应性（AHR）和炎症细胞积聚，为研究两者关系提供实验模型。
比较卵清蛋白致敏的小鼠经鼻内给予 2.5、10、25 或 100μg/只卵清蛋白激发后，AHR 和支气管肺泡灌洗液（BALF）及肺内炎症细胞的积聚情况。
AHR 和炎症细胞积聚均与所用的卵清蛋白激发剂量呈正比。然而，在给予 10μg 卵清蛋白激发的组中，尽管未检测到过敏原诱导的 AHR，但存在气道炎症。进一步分析表明，在该模型中，黏液高分泌或嗜酸性粒细胞脱颗粒与 AHR 的存在均不能相关，而仅在存在 AHR 的组中，BALF 中的白细胞介素（IL）-13 浓度增加。
总之，递增过敏原剂量激发小鼠鼻内可作为研究气道炎症导致过敏原诱导 AHR 的机制的合适实验系统。我们的初步发现与先前的研究结果一致，即 AHR 与嗜酸性粒细胞积聚量分离，并提示 IL-13 在该过程中的作用。
