Thorax 1999;54:488-492 ( June )

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

Robert J Hancox, ^aDavid A Stevens, ^bIan M Adcock, ^bPeter J Barnes, ^bD Robin Taylor^a

^a Department of Respiratory Medicine, Dunedin School of Medicine, University of Otago, New Zealand, ^b National Heart & Lung Institute, London SW3 6LY, UK

Correspondence to: Dr D R Taylor, Department of Medicine, Dunedin School of Medicine, PO Box 913, Dunedin, New Zealand.

Received 2 March 1998; Returned to authors 25 August 1998; Revised version received 11 February 1999; Accepted for publication 11 February 1999

BACKGROUNDInhaled corticosteroids and  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 (NFB). 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  agonist drugs. A study was undertaken to determine whether these interactions occur during treatment with ₂ agonists and corticosteroids in asthma.
METHODSSeven 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 NFB.
RESULTSBudesonide increased GR activity (p<0.05) and decreased NFB activity (p<0.05). No treatment combination altered CREB activity and terbutaline had no significant effects on any transcription factor.
CONCLUSIONSInhaled corticosteroids have significant effects on GR and NFB activity in bronchial mucosa. A negative interaction between inhaled corticosteroids and  agonists was not found.


Keywords: inhaled corticosteroids; ₂ agonists; transcription factors

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© 1999 by Thorax
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