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Azithromycin reduces spontaneous and induced inflammation in DeltaF508 cystic fibrosis mice.
- Source :
-
Respiratory research [Respir Res] 2006 Oct 25; Vol. 7, pp. 134. Date of Electronic Publication: 2006 Oct 25. - Publication Year :
- 2006
-
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.<br />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.<br />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.<br />Conclusion: 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.
- Subjects :
- Animals
Chemokine CXCL2
Interleukin-10 biosynthesis
Lipopolysaccharides
Lung drug effects
Lung pathology
Macrophages drug effects
Macrophages pathology
Mice
Mice, Mutant Strains
Monokines metabolism
Neutrophil Infiltration drug effects
Pneumonia chemically induced
Pneumonia metabolism
Tumor Necrosis Factor-alpha metabolism
Anti-Inflammatory Agents pharmacology
Azithromycin pharmacology
Cystic Fibrosis complications
Cystic Fibrosis genetics
Cystic Fibrosis Transmembrane Conductance Regulator genetics
Pneumonia etiology
Pneumonia pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1465-993X
- Volume :
- 7
- Database :
- MEDLINE
- Journal :
- Respiratory research
- Publication Type :
- Academic Journal
- Accession number :
- 17064416
- Full Text :
- https://doi.org/10.1186/1465-9921-7-134