Azithromycin analogue CSY 0073 attenuates lung inflammation induced by LPS challenge

• Published in: British journal of pharmacology Vol. 171; no. 7; pp. 1783 - 1794
• Main Authors: Balloy, V, Deveaux, A, Lebeaux, D, Tabary, O, le Rouzic, P, Ghigo, J M, Busson, P F, Boëlle, P Y, Guez, J Guez, Hahn, U, Clement, A, Chignard, M, Corvol, H, Burnet, M, Guillot, L
• Format: Journal Article
• Language: English
• Published: 01.04.2014
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/bph.12574

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 CSY 0073. Experimental Approach We compared the effects of CSY 0073 with those of azithromycin in experiments on bacterial cultures, P seudomonas aeruginosa biofilm, lung cells and mice challenged intranasally with P . aeruginosa   LPS . Key Results In contrast to azithromycin, CSY 0073 did not inhibit the growth of P . aeruginosa , S taphylococcus aureus or H aemophilus 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 CSY 0073 and azithromycin (200 mg·kg −1 , i.p.) decreased neutrophil counts at 24 h and TNF ‐α, CXCL 1 and CXCL 2 levels in the BAL fluid after 3 h and IL ‐6, CXCL 2 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. CSY 0073 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, CSY 0073 had no antibacterial effects but it did have a similar anti‐inflammatory profile to that of azithromycin. Hence, CSY 0073 may have potential as a long‐term treatment for patients with chronic lung diseases.