CONICET | Buscador de Institutos y Recursos Humanos

Introduction: High levels of IL-1β, IL-6 and IL-8 have been described in airways of asthmatic patients. It has been shown that stimulation with IL1-β induces the release of IL-6 and IL-8 in the human bronchial cell line Calu-3. This effect decreases with budesonide (BUD-topical steroid), the most used drug for asthma therapy. Previous studies described that nebulized Indomethacin (IN a non-steroidal anti-inflammatory drug) has antiasthmatic properties in humans.Recently microparticles (MPs) carrying IN were developed to deliver this drug to airways as a Dry Powder Inhaler system (DPI).Objetive: The aim of this work was to evaluate if MPs containing IN have effect on the release of IL-6 and IL-8 by stimulated Calu-3 cells and to compare it with raw IN (to assess if MPs excipients influence the IN effect) and with BUD.Materials and Methods: Acidic groups on IN structure were combined with cationic groups of the polyelectrolyte polylysine at 50% neutralization degree and processed by spray-drying to obtain MPs.Calu-3 cells were stimulated by adding IL-1β/H2O2 (50ngml-1/100μM, pro-inflammatory mediators) during 4 hours. Then,cells were divided into control and experimental groups and treated with MPs (20 and 50μM of IN), raw IN (20 and 50μM) and BUD (30μM). After 20 hours treatment, IL-6 and IL-8 released to the supernatant were quantified using a human IL-6 and IL-8 ELISA set.Results: IL-1β/H2O2 exposure increased IL-6 production by 200% and IL-8 by 500%. IL-6 and IL-8 expression was reduced in around 40% when cells were treated with IN MPs, raw IN and BUD. No statistically significant difference was found between materials and concentrations applied (p-value >0.05).Conclusion: IN contained in MPs has the same effect as pure IN andBUD on IL-6 and IL-8 release by inflamed Calu-3 cells.

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