Abstract & Commentary

Azithromycin Restores Chloride Efflux in Cells of Cystic Fibrosis Patients

By Dean L. Winslow, MD, FACP, FIDSA, Chief, Division of AIDS Medicine, Santa Clara Valley Medical Center; Clinical Professor, Stanford University School of Medicine, is Associate Editor for Infectious Disease Alert.

Dr. Winslow is a speaker for GSK and is a consultant for Siemens Diagnostics.

Synopsis: Azithromycin (AZM) was shown to restore chloride (Cl¯) efflux at physiologic concentrations in human bronchial epithelial cells in tissue culture, but did not have anti-inflammatory effects in this system.

Sources: Saint-Criq V, et al. Restoration of chloride efflux by azithromycin in airway epithelial cells of cystic fibrosis patients. Antimicrob Agents Chemother 2011;55:1792-1793.

Two human cystic fibrosis (CF) bronchial epithelial cell lines and one CF human primary epithelial cell line in culture were treated with AZM at 10 µg/mL. Chloride efflux was inhibited significantly in this system as assessed by two different analytical methods. In non-CF cells, AZM significantly inhibited IL-8 secretion and NF-kB activity. However, in CF cells, reduction of IL-8 secretion and NF-kB activity was not seen.


Many protein synthesis-inhibiting antibiotics (most notably tetracyclines and macrolides) have been shown to possess anti-inflammatory activity independent of antimicrobial activity. This anti-inflammatory effect may be in part responsible for the rapid beneficial effect observed in respiratory infections, including acute exacerbations of bronchitis and community-acquired pneumonia. The usefulness of macrolides (particularly AZM) as adjunctive therapy in CF patients has been appreciated for a number of years and their beneficial effect in these diseases was assumed to be due to this anti-inflammatory activity.

CF is a common genetic disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, which encodes a Cl¯ channel. In cystic fibrosis, airway epithelium inflammation is felt to be largely due to an increase in NF-kB activity, which leads to increased IL-8 production. The unexpected results from this in vitro study suggest that the beneficial effects of AZM in CF patients may be due to the drug's effects at one or more steps "upstream" from the inflammatory cascade by restoring CFTR channel activity. Additional research to further elucidate the molecular mechanisms of this observed enhancement of CFTR channel activity will be of great interest.