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Trimethoprim and tetracycline inhibit airway epithelial sodium absorption
P G Middleton1, D M Geddes, E W Alton
1Ion Transport Unit, National Heart and Lung Institute, London, United Kingdom.
Abstract:
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.
Insights
Trimethoprim and tetracycline antibiotics reduce sodium absorption in airway epithelia. This finding is significant for treating chronic lung diseases like cystic fibrosis (CF), potentially offering combined therapeutic effects.
Area of Science:
- Pulmonary Medicine
- Pharmacology
- Cell Physiology
Background:
- Antibiotics are widely used for chronic lung diseases, but their impact on airway mucosa remains unclear.
- Airway epithelial ion transport is crucial for lung health and is dysregulated in conditions like cystic fibrosis.
Purpose of the Study:
- To investigate the effects of various antibiotics on airway epithelial ion transport.
- To identify antibiotics that modulate sodium (Na+) absorption, particularly relevant for cystic fibrosis treatment.
Main Methods:
- In vitro studies using sheep tracheal epithelium to assess electrogenic ion transport.
- In vivo studies in healthy human volunteers and cystic fibrosis patients measuring nasal potential difference.
- Evaluation of antibiotic effects on sodium absorption and response to amiloride.
Main Results:
- Trimethoprim and tetracycline rapidly decreased ion transport in sheep trachea, indicating Na+ absorption inhibition.
- These effects were reversible, mucosal-mediated, and reduced by amiloride.
- In humans, trimethoprim and tetracycline decreased nasal potential difference, with enhanced effects in cystic fibrosis patients.
Conclusions:
- Trimethoprim and tetracycline inhibit airway epithelial sodium absorption.
- These antibiotics may hold potential for combined therapeutic strategies in cystic fibrosis management.