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© J.M. Ghigo (Institut Pasteur) and Brigite Arbeille (LBC-ME. Faculté de Médecine de Tours)
Colorized scanning electron microscopy of an E. coli biofilm developing on a glass surface
Publication : British Journal of Pharmacology

Azithromycin analogue CSY0073 attenuates lung inflammation induced by LPS challenge

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in British Journal of Pharmacology - 01 Apr 2014

Balloy V, Deveaux A, Lebeaux D, Tabary O, le Rouzic P, Ghigo JM, Busson PF, Boëlle PY, Guez JG, Hahn U, Clement A, Chignard M, Corvol H, Burnet M, Guillot L.

Link to Pubmed [PMID] – 24417187

Br J Pharmacol. 2014 Apr;171(7):1783-94

BACKGROUND AND PURPOSE:

Azithromycin is a macrolide antibiotic with anti-inflammatory and immunomodulating effects. Long-term azithromycin therapy in patients with chronic lung diseases such as cystic fibrosis has been associated with increased antimicrobial resistance, emergence of hypermutable strains, ototoxicity and cardiac toxicity. The aim of this study was to assess the anti-inflammatory effects of the non-antibiotic azithromycin derivative CSY0073.

EXPERIMENTAL APPROACH:

We compared the effects of CSY0073 with those of azithromycin in experiments on bacterial cultures, Pseudomonas aeruginosa biofilm, lung cells and mice challenged intranasally with P. aeruginosa LPS.

KEY RESULTS:

In contrast to azithromycin, CSY0073 did not inhibit the growth of P. aeruginosa, Staphylococcus aureus or Haemophilus influenzae and had no effect on an established P. aeruginosa biofilm. Bronchoalveolar lavage (BAL) fluids and lung homogenates collected after the LPS challenge in mice showed that CSY0073 and azithromycin (200 mg·kg(-1), i.p.) decreased neutrophil counts at 24 h and TNF-α, CXCL1 and CXCL2 levels in the BAL fluid after 3 h and IL-6, CXCL2 and IL-1β levels in the lung after 3 h compared with the vehicle. However, only azithromycin reduced IL-1β levels in the lung 24 h post LPS challenge. CSY0073 and azithromycin similarly diminished the production of pro-inflammatory cytokines by macrophages, but not lung epithelial cells, exposed to P. aeruginosa LPS.

CONCLUSIONS AND IMPLICATIONS:

Unlike azithromycin, CSY0073 had no antibacterial effects but it did have a similar anti-inflammatory profile to that of azithromycin. Hence, CSY0073 may have potential as a long-term treatment for patients with chronic lung diseases.

http://www.ncbi.nlm.nih.gov/pubmed/24417187