Effects of inhaled β agonist and corticosteroid treatment on nuclear transcription factors in bronchial mucosa in asthma

Abstract

Background. Inhaled corticosteroids and β agonists are the most commonly used treatments in asthma and are often used together. Recent evidence suggests that many of the anti-inflammatory actions of corticosteroids are mediated by cross-talk between the activated glucocorticoid receptor (GR) and other transcription factors such as the pro-inflammatory nuclear factor kappa B (NFκ-B). Beta agonists can activate the transcription factor cAMP response element binding protein (CREB). A mutual inhibition between GR and CREB occurs in vitro which raises the possibility of a negative interaction between corticosteroid and β agonist drugs. A study was undertaken to determine whether these interactions occur during treatment with β2 agonists and corticosteroids in asthma. Methods. Seven subjects who were participating in a randomised, placebo controlled, crossover study of six weeks treatment with inhaled budesonide (400 μg twice daily), terbutaline (1 mg four times daily), and combined treatment were recruited. Biopsy samples of the bronchial mucosa were obtained after each treatment and analysed for the DNA binding activity of GR, CREB, and NFκB. Results. Budesonide increased GR activity (p < 0.05) and decreased NFκB activity (p < 0.05). No treatment combination altered CREB activity and terbutaline had no significant effects on any transcription factor. Conclusions. Inhaled corticosteroids have significant effects on GR and NFκB activity in bronchial mucosa. A negative interaction between inhaled corticosteroids and β agonists was not found.