Brain-derived neurotrophic factor (BDNF) contributes to neuronal dysfunction in a model of allergic airway inflammation

1 Brain-derived neurotrophic factor (BDNF) is a candidate molecule for mediating functional neuronal changes in allergic bronchial asthma. Recently, enhanced production of BDNF during allergic airway inflammation caused by infiltrating T-cells and macrophages as well as by resident airway epithelial cells has been described. It was the aim of this study to investigate the effect of enhanced BDNF levels on lung function and airway inflammation in a mouse model of allergic inflammation. 2 Ovalbumin-sensitised BALB/c mice were challenged in two consecutive allergen challenges. Prior to the challenge, the mice were treated with either anti-BDNF antibodies or isotype-matched control antibodies. Airway responsiveness to methacholine, capsaicin and electric field stimulation, as well as airway inflammation and chronic airway obstruction 1 week after the last allergen challenge were assessed. 3 Anti-BDNF blocked enhanced reactivity in response to capsaicin, but not airway smooth muscle hyper-reactivity in vivo. Furthermore, persistent airway obstruction, as observed I week after the last allergen challenge, was to a large extent prevented by anti-BDNF treatment. In vitro, BDNF and anti-BDNF treatment had a profound effect on local neuronal hyper-reactivity, as shown by electric field stimulation experiments. In contrast, neither BDNF nor anti-BDNF treatment affected airway inflammation. 4 Our data indicate that development of allergen-induced neuronal hyper-reactivity in mice is partially mediated by BDNF.