Azithromycin increases survival and reduces lung inflammation in cystic fibrosis mice

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. 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. 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. Azithromycin enhances bacterial clearance and reduces lung inflammation by improving innate immune defense mechanisms in CF mice.