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

Purpose: The aim of this study was to assess the effects of low-dose clarithromycin, formulated as pressurised 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.