Effects of Macrolide and Corticosteroid in Neutrophilic Asthma Mouse Model

Tuberculosis and Respiratory Diseases

article

Tai Joon An¹  Chin Kook Rhee²  Ji Hye Kim¹  Young Rong Lee³  Jin Young Chon³  Chan Kwon Park¹  Hyoung Kyu Yoon¹ 

[1] Division of Pulmonary, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea;Division of Pulmonary, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea;Department of Anesthesiology and Pain Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea

关键词: Neutrophils;    Asthma;    Macrolides;    Adrenal Cortex Hormones;    Th17 Cells;    Inflammation;    Histone Deacetylases;   

DOI  :  10.4046/trd.2017.0108

学科分类：医学（综合）

来源: The Korean Academy of Tuberculosis and Respiratory Diseases

【 摘 要 】

Background Asthma is a disease of chronic airway inflammation with heterogeneous features. Neutrophilic asthma is corticosteroid-insensitive asthma related to absence or suppression of TH2 process and increased TH1 and/or TH17 process. Macrolides are immunomodulatory drug that reduce airway inflammation, but their role in asthma is not fully known. The purpose of this study was to evaluate the role of macrolides in neutrophilic asthma and compare their effects with those of corticosteroids. Methods C57BL/6 female mice were sensitized with ovalbumin (OVA) and lipopolysaccharides (LPS). Clarithromycin (CAM) and/or dexamethasone (DXM) were administered at days 14, 15, 21, 22, and 23. At day 24, the mice were sacrificed. Results Airway resistance in the OVA+LPS exposed mice was elevated but was more attenuated after treatment with CAM+DXM compared with the monotherapy group (p<0.05 and p<0.01). In bronchoalveolar lavage fluid study, total cells and neutrophil counts in OVA+LPS mice were elevated but decreased after CAM+DXM treatment. In hematoxylin and eosin stain, the CAM+DXM-treated group showed less inflammation additively than the monotherapy group. There was less total protein, interleukin 17 (IL-17), interferon γ, and tumor necrosis factor α in the CAM+DXM group than in the monotherapy group (p<0.001, p<0.05, and p<0.001). More histone deacetylase 2 (HDAC2) activity was recovered in the DXM and CAM+DXM challenged groups than in the control group (p<0.05). Conclusion Decreased IL-17 and recovered relative HDAC2 activity correlated with airway resistance and inflammation in a neutrophilic asthma mouse model. This result suggests macrolides as a potential corticosteroid-sparing agent in neutrophilic asthma.

【 授权许可】

CC BY-NC