Effect of inhaled hydrosoluble curcumin on inflammatory markers in broncho-alveolar lavage fluid of horses with LPS-induced lung neutrophilia

Background: Horses commonly suffer from chronic respiratory disease and are also used in large animal models of spontaneous or induced airway inflammation. The anti-inflammatory properties of curcumin are largely described but its low bioavailability precludes its clinical use. NDS27, a lysin salt of curcumin incorporated in beta-cyclodextrine, has high bioavailability and can be administered by inhalation. The aim of this study was to investigate the effects of inhaled NDS27 on inflammatory cytokines and proteins in the broncho-alveolar lavage fluid using a model of neutrophilic airway inflammation. Methods: Airway neutrophilia was induced in eight horses by inhalation of lipopolysaccharides (LPS). Horses were treated with either inhalation of NDS27 or with placebo in a randomized cross-over design. Broncho-alveolar lavages were performed 6 hours after stimulation with LPS. Percentage of neutrophils, concentrations of IL-1β, TNF-α, IL-6, Club cell secretory protein, myeloperoxidase (MPO) and elastase (ELT) concentrations were determined. Results: LPS stimulation induced significant increases in neutrophil counts and concentrations of IL-6 (70.2 ± 66.0 pg/ml), TNF-α (43.9 ± 31.2 pg/ml), MPO (580.9 ± 327.0 ng/ml) and ELT (27.6 ± 16.7 ng/ml). Treatment with NDS27 significantly prevented the increase in active and total MPO (216.4 ± 118.1 ng/ml) and ELT (5.9 ± 3.2 ng/ml) while there was a trend towards reduced IL-6 concentration. Conclusions: Results show that, although not reducing neutrophil recruitment, NDS27 largely abolishes LPS-induced neutrophil degranulation. Reduced levels of ELT and MPO, as well as reduced MPO activity may have beneficial effects via a reduced production of reactive oxygen species implicated in chronic inflammation and airway remodeling.