Immunomodulatory activity of vardenafil on induced lung inflammation in cystic fibrosis mice

J Cyst Fibros. 2012 Jul;11(4):266-73. doi: 10.1016/j.jcf.2012.03.003. Epub 2012 Apr 12.

Abstract

Background: We tested the hypothesis that vardenafil, a common drug used for improving erectile dysfunction and able to partially normalize transepithelial chloride transport in cystic fibrosis (CF), modulates CF lung inflammation.

Methods: Inflammatory markers in lungs of F508del-CF and wild-type mice were monitored in response to lipopolysaccharide from Pseudomonas aeruginosa (LPS). The effect of pretreatment with vardenafil (0.14 mg/kg) was evaluated.

Results: A latent inflammatory status, characterized by neutrophil infiltrate, mouse macrophage inflammatory protein (MIP)-2 and tumor necrosis factor (TNF)-α, was found in baseline conditions in F508del-CF mice. Inflammatory markers were increased after LPS with higher responses in CF. Vardenafil globally attenuated inflammatory responses in both genotypes however reduction of macrophage infiltration, macrophage chemoattractant chemokine and interleukin-1β was observed in the CF group only.

Conclusion: Vardenafil reduces lung inflammation with a more pronounced effect in F508del-CF mice, particularly on macrophage cell markers.

MeSH terms

  • Animals
  • Animals, Outbred Strains
  • Cystic Fibrosis / drug therapy*
  • Cystic Fibrosis / genetics
  • Cystic Fibrosis / immunology*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Disease Models, Animal
  • Female
  • Imidazoles / pharmacology*
  • Immunomodulation / drug effects
  • Immunomodulation / immunology
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Macrophages / immunology
  • Macrophages / microbiology
  • Male
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred CFTR
  • Phosphodiesterase 5 Inhibitors / pharmacology
  • Piperazines / pharmacology*
  • Pneumonia / chemically induced
  • Pneumonia / drug therapy*
  • Pneumonia / immunology*
  • Pseudomonas Infections / drug therapy
  • Pseudomonas Infections / immunology
  • Sulfones / pharmacology
  • Triazines / pharmacology
  • Vardenafil Dihydrochloride

Substances

  • Imidazoles
  • Lipopolysaccharides
  • Phosphodiesterase 5 Inhibitors
  • Piperazines
  • Sulfones
  • Triazines
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Vardenafil Dihydrochloride