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Published ahead of print on January 18, 2005, doi:10.1164/rccm.200311-1508OC
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American Journal of Respiratory and Critical Care Medicine Vol 171. pp. 868-871, (2005)
© 2005 American Thoracic Society
doi: 10.1164/rccm.200311-1508OC

Original Article

Effect of Macrolides on In Vivo Ion Transport across Cystic Fibrosis Nasal Epithelium

Pierre M. Barker, Daniel J. Gillie, Michael S. Schechter and Bruce K. Rubin

Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill; Department of Pediatrics, Wake Forest University School of Medicine, Winston-Salem, North Carolina; and Brown Medical School, Providence, Rhode Island

Correspondence and requests for reprints should be addressed to Pierre M. Barker, M.D., Department of Pediatrics, University of North Carolina at Chapel Hill, 200 Mason Farm Road, Chapel Hill, NC 27599-7220. E-mail: pbarker{at}med.unc.edu

Fourteen- and 15-member macrolide antibiotics are under investigation as potential therapeutic agents for cystic fibrosis (CF). The nonantibiotic mechanisms of action of these compounds in CF are not understood. We used nasal potential difference (NPD) measurements to test the effect of macrolides on airway epithelial ion (chloride, sodium) transport of CF mice and humans. We tested clarithromycin and azithromycin in mice, and clarithromycin in patients with CF. Baseline and post-treatment NPD was measured in two strains (C57Bl6 and BalbC) of CF transmembrane regulator "knockout" and littermate control mice, and in {Delta}F508/{Delta}F508 mice. In addition, NPD was measured in 18 human subjects with CF (17 {Delta}F-508/{Delta}F-508 and 1 {Delta}F-508/other) who were undergoing a 12-month, randomized, double-blind crossover study of the effects of clarithromycin on pulmonary outcome in CF. Neither clarithromycin nor azithromycin affected ion transport characteristics of normal or CF nasal epithelium in either mouse or humans. We conclude that the apparent beneficial effects of macrolides on pulmonary outcome in CF are not mediated by their modulation of ion transport.

Key Words: antibiotic • chloride • nasal potential difference • therapy




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