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

Charlotte Sandersen; Dorothee Bienzle; Simona Cerri; Thierry Franck; Sandrine Derochette; Philippe Neven; Ange Mouytis-Mickalad; Didier Serteyn

doi:10.4081/mrm.2015.290

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

Authors

Charlotte Sandersen Equine Clinic, Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Liège, Liège, Belgium
Dorothee Bienzle Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON
Simona Cerri Equine Clinic, Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Liège, Liège, Belgium
Thierry Franck Equine Clinic, Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Liège, Liège, Belgium
Sandrine Derochette Center for Oxygen Research and Development, University of Liege
Philippe Neven 3Center for Oxygen Research and Development, University of Liege,
Ange Mouytis-Mickalad Center for Oxygen Research and Development, University of Liege,
Didier Serteyn Equine Clinic, Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Liège; 3Center for Oxygen Research and Development, University of Liege,

DOI: https://doi.org/10.4081/mrm.2015.290

Keywords:

Airway inflammation, Large animal model, Lipopolysaccharide, Curcumin, NDS27

Abstract

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.