Budesonide and formoterol inhibit inflammatory mediator production by bronchial epithelial cells infected with rhinovirus

Clin Exp Allergy. 2009 Nov;39(11):1700-10. doi: 10.1111/j.1365-2222.2009.03307.x. Epub 2009 Jun 22.


Background: Rhinoviruses (RVs) are responsible for the majority of acute asthma and chronic obstructive pulmonary disease (COPD) exacerbations. RVs infect the lower airways and induce the production of pro-inflammatory and remodelling-associated mediators. Budesonide (BUD) and formoterol (FORM) synergize in controlling asthma and COPD exacerbations; however, their effects on virus-induced inflammation and remodelling are less known.

Objective: We investigated whether BUD and FORM synergize in suppressing RV-induced inflammation and remodelling in the airways.

Methods: In vitro models of RV infection of BEAS-2B and primary normal human bronchial epithelial (NHBE) cells were used. We assessed the effects of individual and combined drugs administered post-infection, at a clinically relevant concentration range (10(-6)-10(-10) m), on the production of CCL5, CXCL10, CXCL8, IL-6 and the remodelling-associated VEGF and bFGF, using ELISA and RT-PCR.

Results: BUD effectively suppressed RV-mediated induction of all mediators studied, in a concentration-dependent manner. FORM alone suppressed the production of CXCL8 and bFGF. The combination of BUD and FORM had concentration-dependent, additive or synergistic effects in the suppression of RV-induced CCL5, CXCL8 and CXCL10 in both cell types as well as VEGF in NHBE only. Combination treatment also resulted in an enhanced suppression of RV-induced IL-6, and CCL5 at the mRNA level as compared with BUD or FORM alone.

Conclusion: BUD and FORM suppress RV-induced chemokines and growth factors in bronchial epithelial cells in a concentration-dependent, synergistic or additive manner. These data further support the combined use of BUD and FORM in asthma and COPD and intensification of this therapy during exacerbations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asthma / drug therapy
  • Asthma / metabolism
  • Bronchi / metabolism*
  • Bronchi / virology
  • Bronchodilator Agents / agonists
  • Bronchodilator Agents / pharmacology*
  • Bronchodilator Agents / therapeutic use
  • Budesonide / agonists
  • Budesonide / pharmacology*
  • Budesonide / therapeutic use
  • Chemokine CXCL10 / biosynthesis
  • Chemokines / biosynthesis
  • Drug Synergism
  • Epithelial Cells / metabolism*
  • Epithelial Cells / virology
  • Ethanolamines / agonists
  • Ethanolamines / pharmacology*
  • Ethanolamines / therapeutic use
  • Fibroblast Growth Factor 2 / biosynthesis
  • Formoterol Fumarate
  • Humans
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Inflammation Mediators / metabolism*
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Picornaviridae Infections / drug therapy*
  • Picornaviridae Infections / metabolism
  • Pulmonary Disease, Chronic Obstructive / drug therapy
  • Pulmonary Disease, Chronic Obstructive / metabolism
  • Respiratory Mucosa / metabolism*
  • Respiratory Mucosa / virology
  • Rhinovirus*
  • Vascular Endothelial Growth Factor A / biosynthesis


  • Bronchodilator Agents
  • CXCL10 protein, human
  • Chemokine CXCL10
  • Chemokines
  • Ethanolamines
  • Inflammation Mediators
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 2
  • Intercellular Adhesion Molecule-1
  • Budesonide
  • Formoterol Fumarate