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Published on: May 12, 2020
Azithromycin increases survival and reduces lung inflammation in cystic fibrosis mice
Wan C Tsai1, Marc B Hershenson, Ying Zhou
1Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI 48105, USA.
Objective And Design:
Azithromycin (AZM) has been used as an anti-inflammatory agent in the treatment of cystic fibrosis (CF), particularly those with chronic infection with P. aeruginosa (PA). To investigate mechanisms associated with the beneficial effects of AZM in CF, we examined bacterial load, cytokine levels, and clearance of inflammatory cells in CF mice infected with mucoid PA and treated with AZM.
Methods:
Gut-corrected Cftr(tm1Unc)-TgN(FABPCFTR)#Jaw CF mice infected with an alginate-overproducing PA CF-isolate were treated with AZM or saline and examined for survival of animals, lung bacterial load, inflammation, cytokine levels, and apoptotic cells up to 5 days post-infection.
Results:
Administration of AZM (20 mg/kg) 24 h after the infection improved 5-day survival to 95% compared with treatment with saline (56%). AZM administration was associated with significant reductions in bacterial load, decreased lung inflammation, and increased levels of IFN-gamma. AZM increased macrophage clearance of apoptotic neutrophils from the lung.
Conclusion:
Azithromycin enhances bacterial clearance and reduces lung inflammation by improving innate immune defense mechanisms in CF mice.
Insights
Azithromycin (AZM) treatment improved survival in cystic fibrosis (CF) mice infected with Pseudomonas aeruginosa (PA). AZM reduced bacterial load and lung inflammation by enhancing immune defenses.
Area of Science:
- Pulmonary Medicine
- Microbiology
- Immunology
Background:
- Cystic Fibrosis (CF) is characterized by chronic Pseudomonas aeruginosa (PA) infection and inflammation.
- Azithromycin (AZM) is used for its anti-inflammatory effects in CF patients with PA infection.
Purpose of the Study:
- To investigate the mechanisms behind AZM's beneficial effects in CF.
- To assess AZM's impact on bacterial load, cytokine levels, and inflammatory cell clearance in a CF mouse model.
Main Methods:
- CF mice infected with mucoid PA were treated with AZM or saline.
- Evaluated survival, lung bacterial load, inflammation, cytokine levels (IFN-gamma), and apoptotic cells.
Main Results:
- AZM treatment significantly increased 5-day survival (95% vs. 56% with saline).
- AZM reduced bacterial load, lung inflammation, and increased IFN-gamma levels.
- AZM enhanced macrophage clearance of apoptotic neutrophils.
Conclusions:
- Azithromycin enhances bacterial clearance in CF mice.
- AZM reduces lung inflammation by improving innate immune defenses.
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