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Azithromycin increases survival and reduces lung inflammation in cystic fibrosis mice

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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 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-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.

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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

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Acknowledgments

We thank Dr. N. Hoffmann, University of Copenhagen for providing us MPA isolate used in this study. We thank Dr. van Heeckeren, Case Western Reserve University, Cleaveland, Ohio for providing Gut-corrected CF mice. This work was supported by the Cystic Fibrosis Foundation.

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Authors and Affiliations

  1. Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI, 48105, USA

    Wan C. Tsai, Marc B. Hershenson, Ying Zhou & Umadevi Sajjan

  2. Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48105, USA

    Marc B. Hershenson

  3. University of Michigan, 1150 W. Medical Center Dr., Room 3570, MSRBII, Box 5688, Ann Arbor, MI, 48109-0688, USA

    Umadevi Sajjan

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  1. Wan C. Tsai
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  2. Marc B. Hershenson
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Correspondence to Umadevi Sajjan.

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Responsible Editor: M. Parnham.

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Tsai, W.C., Hershenson, M.B., Zhou, Y. et al. Azithromycin increases survival and reduces lung inflammation in cystic fibrosis mice. Inflamm. Res. 58, 491–501 (2009). https://doi.org/10.1007/s00011-009-0015-9

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  • DOI: https://doi.org/10.1007/s00011-009-0015-9

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