Am. J. Respir. Crit. Care Med., Volume 157, Number 3, March 1998, 803-809

Albuterol Does Not Antagonize the Inhibitory Effect of Dexamethasone on Monocyte Cytokine Release

PAUL M. SELDON, DAVID A. STEVENS, IAN M. ADCOCK, BRIAN J. O'CONNOR, PETER J. BARNES, and MARK A. GIEMBYCZ

Thoracic Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, London; and Department of Thoracic Medicine, King's College Hospital, London, United Kingdom

₂-Adrenoceptor agonists given by the inhaled route are the most effective bronchodilators known, yet high doses of these drugs may be associated with an increase in asthma mortality and morbidity. One theory for this paradox is that chronic use of ₂-adrenoceptor agonists compromises the anti- inflammatory action of glucocorticosteroids. This hypothesis derives from the ability of albuterol and fenoterol to inhibit the interaction of the glucocorticosteroid receptor (GR) with proinflammatory transcriptional activators acting on the promoter region of certain target genes that encode cytokines such as tumor necrosis factor- (TNF) and granulocyte/macrophage colony-stimulating factor (GM-CSF). However, the functional relevance of these results has not been formally investigated. We have tested the hypothesis that albuterol reduces the ability of dexamethasone to inhibit the generation of TNF and GM-CSF from lipopolysaccharide (LPS)-stimulated human monocytes. Pretreatment of human monocytes with albuterol (1 and 100 µM) for 5 and for 180 min inhibited maximally TNF generation by approximately 25%. However, regardless of the concentration of albuterol, or the time of preincubation, the inhibitory effect of dexamethasone was not significantly affected with respect to the EC₅₀ or the maximal effect produced. Qualitatively identical data were obtained when GM-CSF release was used as an index of monocyte activation. We conclude that high concentrations of albuterol do not compromise the ability of dexamethasone to suppress the generation of TNF and GM-CSF from LPS-stimulated human monocytes.

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