Inflammation Research

, Volume 58, Issue 8, pp 491–501

Azithromycin increases survival and reduces lung inflammation in cystic fibrosis mice

  • Wan C. Tsai
  • Marc B. Hershenson
  • Ying Zhou
  • Umadevi Sajjan
Original Research Paper

DOI: 10.1007/s00011-009-0015-9

Cite this article as:
Tsai, W.C., Hershenson, M.B., Zhou, Y. et al. Inflamm. Res. (2009) 58: 491. doi:10.1007/s00011-009-0015-9

Abstract

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 Cftrtm1Unc-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-γ. 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.

Keywords

P. aeruginosaLung infectionMacrolideMacrophageInnate immunity

Abbreviations

CF

Cystic fibrosis

PA

P. aeruginosa

MPA

Mucoid P. aeruginosa

AZM

Azithromycin

KC

Mouse growth-related oncogene-α

MCP-1

Monocyte chemoattractant protein-1

Copyright information

© Birkhäuser Verlag, Basel/Switzerland 2009

Authors and Affiliations

  • Wan C. Tsai
    • 1
  • Marc B. Hershenson
    • 1
    • 2
  • Ying Zhou
    • 1
  • Umadevi Sajjan
    • 1
    • 3
  1. 1.Department of Pediatrics and Communicable DiseasesUniversity of MichiganAnn ArborUSA
  2. 2.Department of Molecular and Integrative PhysiologyUniversity of MichiganAnn ArborUSA
  3. 3.University of MichiganAnn ArborUSA