Sandersen Charlotte, Bienzle Dorothee, Cerri Simona, Franck Thierry, Derochette Sandrine, Neven Philippe, Mouytis-Mickalad Ange, Serteyn Didier
Equine Clinic, Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.
Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1 Canada.
Multidiscip Respir Med. 2015 Apr 15;10(1):16. doi: 10.1186/s40248-015-0010-7. eCollection 2015.
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.
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.
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.
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.
马常患慢性呼吸道疾病，也被用于自发性或诱导性气道炎症的大型动物模型。姜黄素的抗炎特性已有大量描述，但其低生物利用度限制了其临床应用。NDS27是一种包合在β-环糊精中的姜黄素赖氨酸盐，具有高生物利用度，可通过吸入给药。本研究旨在使用嗜中性气道炎症模型，研究吸入NDS27对支气管肺泡灌洗液中炎性细胞因子和蛋白质的影响。
通过吸入脂多糖（LPS）诱导8匹马发生气道嗜中性粒细胞增多。采用随机交叉设计，对马进行吸入NDS27或安慰剂治疗。在LPS刺激6小时后进行支气管肺泡灌洗。测定中性粒细胞百分比、白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、克拉拉细胞分泌蛋白、髓过氧化物酶（MPO）和弹性蛋白酶（ELT）的浓度。
LPS刺激导致中性粒细胞计数以及IL-6（70.2±66.0 pg/ml）、TNF-α（43.9±31.2 pg/ml）、MPO（580.9±327.0 ng/ml）和ELT（27.6±16.7 ng/ml）浓度显著增加。NDS27治疗显著抑制了活性MPO和总MPO（216.4±118.1 ng/ml）以及ELT（5.9±3.2 ng/ml）的增加，同时IL-6浓度有降低趋势。
结果表明，尽管NDS27不能减少中性粒细胞募集，但能在很大程度上消除LPS诱导的中性粒细胞脱颗粒。ELT和MPO水平降低以及MPO活性降低，可能通过减少与慢性炎症和气道重塑相关的活性氧生成而产生有益作用。
