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Immunomodulatory effects of a low-dose clarithromycin-based macrolide solution pressurised metered dose inhaler
Mehra Haghi1, Alessandro Saadat, Bing Zhu
1Respiratory Technology Woolcock Institute of Medical Research and Discipline of Pharmacology, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
Purpose:
The aim of this study was to assess the effects of low-dose clarithromycin, formulated as solution pressurized metered dose inhaler, following deposition on the Calu-3 respiratory epithelial cells.
Methods:
Clarithromycin was deposited on the air-interface culture of Calu-3 cells using a modified Andersen cascade impactor. Transport of fluorescein-Na, production of mucus and interleukin-8 release from Calu-3 cells following stimulation with transforming growth factor-β and treatment with clarithromycin was investigated.
Results:
The deposition of clarithromycin had significant effect on the permeability of fluorescein-Na, suggesting that the barrier integrity was improved following a short-term treatment with clarithromycin (apparent permeability values were reduced to 3.57 × 10(-9) ± 2.32 × 10(-9) cm.s(-1), compared to 1.14 × 10(-8) ± 4.30 × 10(-8) cm.s(-1) for control). Furthermore, the amount of mucus produced was significantly reduced during the course of clarithromycin treatment. The concentration of interleukin-8 secreted from Calu-3 cells following stimulation with transforming growth factor-β resulted in significantly lower level of interleukin-8 released from the cells pre-treated with clarithromycin (5.2 ± 0.5 ng.ml(-1) clarithromycin treated vs. 7.7 ± 0.8 ng.ml(-1) control, respectively).
Conclusions:
Our data demonstrate that treatment with clarithromycin decreases the paracellular permeability of epithelial cells, mucus secretion and interleukin-8 release and therefore, inhaled clarithromycin holds potential as an anti-inflammatory therapy.
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