Is interleukin-13 critical in maintaining airway hyperresposiveness in allergen-challenged mice?
Is interleukin-13 critical in maintaining airway hyperresposiveness in allergen-challenged mice?
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DOI：
10.1164/rccm.200311-1488oc
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发表时间：
2004-10-15
影响因子：
24.7
通讯作者：
Inman, MD
中科院分区：
文献类型：
--
作者：
Leigh, R;Ellis, R;Inman, MD
白细胞介素（IL）-13被认为是气道高反应性病理生理学中的中枢效应物。我们已经描述了一种小鼠模型，其中慢性过敏原暴露导致持续的气道高反应性和气道重塑的各个方面，并在此试图证明气道高反应性的这一组成部分是独立的生物活性IL-13。致敏小鼠经历短暂或长期的过敏原暴露，并在短暂或慢性过敏原吸入后24小时或4周进行研究。在两个方案中，在结果测量日之前的4天期间，每天给予特异性结合并中和IL-13的可溶性鼠抗IL-13受体融合蛋白。结果测量包括气道反应静脉注射美沙胆碱，支气管肺泡灌洗液细胞计数，和气道形态。与生理盐水对照组相比，短暂的过敏原激发导致气道高反应性，抗IL-13治疗可以预防。慢性过敏原激发导致持续气道高反应性和气道重塑指数; IL-13阻断未能逆转这种持续气道高反应性。这些结果证实IL-13对于与短暂变应原暴露相关的气道高反应性的发展是关键的，但对于维持与气道重塑相关的持续气道高反应性不是必需的。
Interleukin (IL)-13 is regarded as being a central effector in the pathophysiology of airway hyperresponsiveness. We have described a mouse model in which chronic allergen exposure results in sustained airway hyperresponsiveness and aspects of airway remodeling, and here sought to demonstrate that this component of airway hyperresponsiveness is independent of biologically active IL-13. Sensitized mice were subjected to either brief or chronic periods of allergen exposure and studied 24 hours after brief or 4 weeks after chronic allergen inhalation. A soluble murine anti-IL-13 receptor fusion protein that specifically binds to and neutralizes IL-13 was given daily during the 4 days before the day of outcome measurements in both protocols. Outcome measurements included airway responses to intravenous methachollne, bronchoalveolar lavage fluid cell counts, and airway morphometry. Compared with the saline control, brief allergen challenge resulted in airway hyperresponsiveness, which was prevented by anti-IL-13 treatment. Chronic allergen challenge resulted in sustained airway hyperresponsiveness and indices of airway remodeling; IL-13 blockade failed to reverse this sustained airway hyperresponsiveness. These results confirm that IL-13 is critical for the development of airway hyperresponsiveness associated with brief allergen exposure, but is not necessary to maintain the sustained airway hyperresponsiveness associated with airway remodeling.