title: Azithromycin reduces spontaneous and induced inflammation in DeltaF508 cystic fibrosis mice.
abstract: BACKGROUND
  Inflammation plays a critical role in lung disease development and progression in cystic fibrosis. Azithromycin is used for the treatment of cystic fibrosis lung disease, although its mechanisms of action are poorly understood. We tested the hypothesis that azithromycin modulates lung inflammation in cystic fibrosis mice.
  
  
  METHODS
  We monitored cellular and molecular inflammatory markers in lungs of cystic fibrosis mutant mice homozygous for the DeltaF508 mutation and their littermate controls, either in baseline conditions or after induction of acute inflammation by intratracheal instillation of lipopolysaccharide from Pseudomonas aeruginosa, which would be independent of interactions of bacteria with epithelial cells. The effect of azithromycin pretreatment (10 mg/kg/day) given by oral administration for 4 weeks was evaluated.
  
  
  RESULTS
  In naive cystic fibrosis mice, a spontaneous lung inflammation was observed, characterized by macrophage and neutrophil infiltration, and increased intra-luminal content of the pro-inflammatory cytokine macrophage inflammatory protein-2. After induced inflammation, cystic fibrosis mice combined exaggerated cellular infiltration and lower anti-inflammatory interleukin-10 production. In cystic fibrosis mice, azithromycin attenuated cellular infiltration in both baseline and induced inflammatory condition, and inhibited cytokine (tumor necrosis factor-alpha and macrophage inflammatory protein-2) release in lipopolysaccharide-induced inflammation.
  
  
  CONCLUSIONS
  Our findings further support the concept that inflammatory responses are upregulated in cystic fibrosis. Azithromycin reduces some lung inflammation outcome measures in cystic fibrosis mice. We postulate that some of the benefits of azithromycin treatment in cystic fibrosis patients are due to modulation of lung inflammation.
authors.affiliation: Clinical Chemistry, Université Catholique de Louvain, Ave Hippocrate 10, Brussels, Belgium. rlegssyer@yahoo.fr
authors.forename: Rachida
authors.initials: R
authors.lastname: Legssyer
authors.forename: François
authors.initials: F
authors.lastname: Huaux
authors.forename: Jean
authors.initials: J
authors.lastname: Lebacq
authors.forename: Monique
authors.initials: M
authors.lastname: Delos
authors.forename: Etienne
authors.initials: E
authors.lastname: Marbaix
authors.forename: Patrick
authors.initials: P
authors.lastname: Lebecque
authors.forename: Dominique
authors.initials: D
authors.lastname: Lison
authors.forename: Bob J
authors.initials: BJ
authors.lastname: Scholte
authors.forename: Pierre
authors.initials: P
authors.lastname: Wallemacq
authors.forename: Teresinha
authors.initials: T
authors.lastname: Leal
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology*; D054426:Chemokine CXCL2; D003550:Cystic Fibrosis / Q000150:complications* / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D016753:Interleukin-10 / Q000096:biosynthesis; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D015846:Monokines / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D011014:Pneumonia / Q000139:chemically induced / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D054426:Chemokine CXCL2; D008070:Lipopolysaccharides; D015846:Monokines; D014409:Tumor Necrosis Factor-alpha; C093349:cystic fibrosis transmembrane conductance regulator delta F508; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D016753:Interleukin-10; D017963:Azithromycin