Synergistic effects of fluticasone propionate and salmeterol on inhibiting rhinovirus-induced epithelial production of remodelling-associated growth factors

Clin Exp Allergy. 2006 Oct;36(10):1268-73. doi: 10.1111/j.1365-2222.2006.02566.x.

Abstract

Background: Rhinoviruses (RV), the major trigger of acute asthma exacerbations, are able to infect bronchial epithelium and induce production of pro-inflammatory, but also angiogenic and pro-fibrotic mediators. Fluticasone propionate (FP) and salmeterol (S) are clinically effective and act synergistically in controlling persistent asthma; however, their effect on virus-associated asthma is less clear.

Aim: The aim of this study was to assess the individual and combined effects of FP and S on RV-induced epithelial production of vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2).

Methods: Bronchial epithelial cells (BEAS-2B) were exposed in vitro to RV and were subsequently treated with FP and S, at physiologically relevant concentrations, alone or in combination. VEGF and FGF-2 were measured in the supernatants of these cultures using ELISA.

Results: FP was able to reduce RV-induced VEGF production in a dose-dependent manner. S also induced a smaller reduction; addition of both factors inhibited VEGF synergistically. FGF-2 production was not inhibited by either FP or S alone, but was significantly reduced when both substances were present in the culture.

Conclusion: This study demonstrates that FP and S may synergistically inhibit the production of angiogenic and/or pro-fibrotic factors that are induced after RV infection of BEAS-2B and are implicated in airway remodelling, suggesting that this combination may represent an important therapeutic option on virus-induced asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albuterol / analogs & derivatives*
  • Albuterol / therapeutic use
  • Androstadienes / therapeutic use*
  • Anti-Inflammatory Agents / therapeutic use*
  • Bronchi / metabolism*
  • Bronchi / pathology
  • Bronchi / virology
  • Cell Line
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Enzyme-Linked Immunosorbent Assay
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology
  • Epithelial Cells / virology
  • Fibroblast Growth Factor 2 / analysis
  • Fibroblast Growth Factor 2 / metabolism
  • Fluticasone
  • HeLa Cells
  • Humans
  • Intercellular Signaling Peptides and Proteins / analysis
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Picornaviridae Infections / drug therapy
  • Picornaviridae Infections / metabolism
  • Picornaviridae Infections / pathology
  • Rhinovirus
  • Salmeterol Xinafoate
  • Vascular Endothelial Growth Factor A / analysis
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Androstadienes
  • Anti-Inflammatory Agents
  • Intercellular Signaling Peptides and Proteins
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 2
  • Salmeterol Xinafoate
  • Fluticasone
  • Albuterol