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Published ahead of print on January 18, 2005, doi:10.1164/rccm.200311-1508OC

Am. J. Respir. Crit. Care Med., Volume 171, Number 8, April 2005, 868-871

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Submitted on November 6, 2003
Accepted on January 5, 2005

Effect of Macrolides on in vivo Ion Transport Across Cystic Fibrosis Nasal Epithelium

Pierre M Barker1*, Daniel J Gillie1, Michael S Schechter2, and Bruce K Rubin3

1 Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 2 Department of Pediatrics, Brown Medical School, Providence, RI, USA, 3 Department of Pediatrics, Wake Forest University, Winston Salem, NC, USA

* To whom correspondence should be addressed. 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 non-antibiotic 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 CF patients. Baseline and post-treatment NPD was measured in 2 strains (C57Bl6 and BalbC) of cystic fibrosis transmembrane regulator (CFTR) [[TILDE]]knockout[[TILDE]] and littermate control mice, and in {Delta}F508 /{Delta}F508 mice. In addition NPD was measured in 18 CF human subjects (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 man. 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: therapy, nasal potential difference, antibiotic




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