Multiple dosing of simvastatin inhibits airway mucus production of epithelial cells: Implications in the treatment of chronic obstructive airway pathologies

Background: Chronic obstructive pulmonary disease (COPD) is characterised by mucus hyper-production. This pathology, together with other inflammatory contributions, leads to airway obstruction and breath- ing complications. Newer therapeutic approaches are of increased interest, including the use of HMG-CoA reductase inhibitors. Retrospective studies have shown that statins are effective in reducing patient mor- tality and blood cytokines levels. These findings suggest statins may also provide a new therapeutic approach in COPD treatment. Purpose: The aim of the present work was to study the transport of simvastatin (SV) across Calu-3 epi- thelial cells and to investigate its pharmacological action with respect to reduction in mucus production. Methods: Calu-3 cells were grown under liquid covered culture (LCC) conditions for transport studies in order to demonstrate the ability of SV to transport across the monolayer. For mucus detection, cells were grown under air interface culture (AIC) conditions. Samples collected for microscope analysis were stained with alcian blue; images of the stained cell surface were acquired and the mucus was quantified as the RGBB ratio. Results: SV was transported through the cell monolayer and ‘retained’ inside the Calu-3 cells. Colour analysis of stained Calu-3 monolayers microscope-images showed that chronic administration of SV for 14 days caused a significant inhibition in mucus production. Conclusion: These findings suggest that local delivery of SV directly to the lungs may provide a promising treatment and potential disease management approach of COPD, with significant effects on mucus reduction.