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

Am J Respir Crit Care Med. 1998 Mar;157(3 Pt 1):803-9. doi: 10.1164/ajrccm.157.3.9707116.

Abstract

Beta2-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 beta2-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-alpha (TNF alpha) 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 alpha and GM-CSF from lipopolysaccharide (LPS)-stimulated human monocytes. Pretreatment of human monocytes with albuterol (1 and 100 microM) for 5 and for 180 min inhibited maximally TNF alpha 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 alpha and GM-CSF from LPS-stimulated human monocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Agonists / administration & dosage
  • Adrenergic beta-Agonists / pharmacology*
  • Albuterol / administration & dosage
  • Albuterol / pharmacology*
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology*
  • Asthma / drug therapy
  • Asthma / physiopathology
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / pharmacology*
  • Cells, Cultured
  • Cytokines / drug effects*
  • Cytokines / genetics
  • Cytokines / metabolism
  • Dexamethasone / administration & dosage
  • Dexamethasone / pharmacology*
  • Dose-Response Relationship, Drug
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / pharmacology*
  • Granulocyte-Macrophage Colony-Stimulating Factor / drug effects
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Humans
  • Inflammation Mediators / pharmacology
  • Least-Squares Analysis
  • Lipopolysaccharides / pharmacology
  • Monocytes / drug effects*
  • Monocytes / metabolism
  • Promoter Regions, Genetic / drug effects
  • Receptors, Glucocorticoid / antagonists & inhibitors
  • Regression Analysis
  • Transcription, Genetic / drug effects
  • Tumor Necrosis Factor-alpha / drug effects
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Adrenergic beta-Agonists
  • Anti-Inflammatory Agents
  • Bronchodilator Agents
  • Cytokines
  • Glucocorticoids
  • Inflammation Mediators
  • Lipopolysaccharides
  • Receptors, Glucocorticoid
  • Tumor Necrosis Factor-alpha
  • Dexamethasone
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Albuterol