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

Background-Inhaled corticosteroids and beta agonists are the most commonly used treatments in asthma and are often used together. Recent evidence sugg ests that many of the anti-inflammatory actions of corticosteroids are medi ated by cross-talk between the activated glucocorticoid receptor (GR) and o ther transcription factors such as the pro-inflammatory nuclear factor kapp a B (NF kappa 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 interactio n between corticosteroid and beta agonist drugs. A study was undertaken to determine whether these interactions occur during treatment with beta(2), a gonists and corticosteroids in asthma. Methods-Seven subjects who were participating in a randomised, placebo cont rolled, crossover study of six weeks treatment with inhaled budesonide (400 mu g twice daily), terbutaline (1 mg four times daily), and combined treat ment were recruited. Biopsy samples of the bronchial mucosa were obtained a fter each treatment and analysed for the DNA binding activity of GR, CREB, and NF kappa B. Results-Budesonide increased GR activity (p<0.05) and decreased NF kappa B activity p<0.05). No treatment combination altered CREB activity and terbut aline had no significant effects on any transcription factor. Conclusions-Inhaled corticosteroids have significant effects on GR and NF k appa B activity in bronchial mucosa. A negative interaction between inhaled corticosteroids and beta agonists was not found.