Braun A, Lommatzsch M, Lewin G R, Virchow J C, Renz H
Institute of Laboratory Medicine, Campus Virchow, Berlin, Germany.
Int Arch Allergy Immunol. 1999 Feb-Apr;118(2-4):163-5. doi: 10.1159/000024056.
Bronchial asthma (BA) is characterized by a unique type of airway inflammation, epithelial cell damage and increased airway smooth muscle (ASM) contractility. The regulatory network between the immunological events and the neuronal control of ASM contractility remains to be defined.
Utilizing a well-characterized mouse model of airway inflammation and BA, we analyzed the production and function of neurotrophins in allergic asthma. To confirm these data in humans, segmental allergen provocation was performed in mild asthmatics.
Allergen-induced airway inflammation was associated with increased local production of the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in mice as well as in humans. In bronchoalveolar lavage fluid (BALF), NGF levels were increased 4- to 5-fold in men and mice 1 day after allergen provocation. The increase in BDNF was about 2-fold in both models. Treatment of mice with anti-NGF prevented development of airway hyperresponsiveness (AHR). In the human study group, NGF levels in BALF after allergen provocation were correlated significantly with baseline FEV1 levels.
These data strongly suggest that neurotrophins serve as a link between airway inflammation and neuronal control of ASM constriction in BA.
支气管哮喘（BA）的特征是一种独特类型的气道炎症、上皮细胞损伤以及气道平滑肌（ASM）收缩性增加。免疫事件与ASM收缩性的神经控制之间的调节网络仍有待确定。
利用一种特征明确的气道炎症和BA小鼠模型，我们分析了变应性哮喘中神经营养因子的产生和功能。为了在人类中证实这些数据，对轻度哮喘患者进行了节段性变应原激发试验。
变应原诱导的气道炎症与小鼠和人类中神经营养因子神经生长因子（NGF）和脑源性神经营养因子（BDNF）的局部产生增加有关。在支气管肺泡灌洗液（BALF）中，变应原激发后1天，男性和小鼠的NGF水平增加了4至5倍。在两个模型中，BDNF的增加约为2倍。用抗NGF治疗小鼠可预防气道高反应性（AHR）的发展。在人类研究组中，变应原激发后BALF中的NGF水平与基线FEV1水平显著相关。
这些数据强烈表明，神经营养因子在BA中作为气道炎症与ASM收缩的神经控制之间的联系。
