Am. J. Respir. Crit. Care Med., Vol 154, No. 1, 07 1996, 18-23.
Trimethoprim and tetracycline inhibit airway epithelial sodium absorption
PG Middleton, DM Geddes and EW Alton
Ion Transport Unit, National Heart and Lung Institute, London, United Kingdom.
Despite their frequent use in the treatment of chronic lung disease, the
effect of antibiotics on the airway mucosa has not been defined. We have
assessed the effect of a number of antibiotics on the ion transport
processes of airway epithelia. Initial evaluation performed on sheep
tracheal epithelium in vitro demonstrated that trimethoprim and
tetracycline induced a rapid decrease in electrogenic ion transport. These
responses were fully reversible, mediated through the mucosal surface, and
reduced by amiloride pretreatment, suggesting inhibition of Na+ absorption.
Serosal application of erythromycin produced a gradual decrease in
short-circuit current, whereas other antibiotics (ampicillin, ceftazidime,
colistin, chloramphenicol, gentamicin, and sulfamethoxazole) caused no
significant change within 30 min of addition. In healthy human volunteers,
trimethoprim and tetracycline induced a rapid decrease in nasal potential
difference, which was attenuated by amiloride pretreatment. In subjects
with cystic fibrosis, who exhibit increased Na+ absorption across
respiratory epithelia, the responses to trimethoprim and tetracycline were
enhanced, providing further evidence that these drugs inhibit Na+
absorption. In conclusion, this study has identified two antibacterial
agents that also reduce the Na+ absorption found in CF. These drugs may
offer combined effects for the treatment of CF.
