Neurotrophins: A Link between Airway Inflammation and Airway Smooth Muscle Contractility in Asthma?

Abstract

Background: 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. Methods: 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. Results: 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. Conclusion: These data strongly suggest that neurotrophins serve as a link between airway inflammation and neuronal control of ASM constriction in BA.