Immunomodulatory Effects of a Low-Dose Clarithromycin-Based Macrolide Solution Pressurised Metered Dose Inhaler

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. 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-beta and treatment with clarithromycin was investigated. 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 x 10(-9) +/- 2.32 x 10(-9) cm.s(-1), compared to 1.14 x 10(-8) +/- 4.30 x 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-beta 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). 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.