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Effects of Macrolide and Corticosteroid in Neutrophilic Asthma Mouse Model

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 inflamm...

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Autores principales: An, Tai Joon, Rhee, Chin Kook, Kim, Ji Hye, Lee, Young Rong, Chon, Jin Young, Park, Chan Kwon, Yoon, Hyoung Kyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Academy of Tuberculosis and Respiratory Diseases 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5771750/
https://www.ncbi.nlm.nih.gov/pubmed/29332324
http://dx.doi.org/10.4046/trd.2017.0108
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author An, Tai Joon
Rhee, Chin Kook
Kim, Ji Hye
Lee, Young Rong
Chon, Jin Young
Park, Chan Kwon
Yoon, Hyoung Kyu
author_facet An, Tai Joon
Rhee, Chin Kook
Kim, Ji Hye
Lee, Young Rong
Chon, Jin Young
Park, Chan Kwon
Yoon, Hyoung Kyu
author_sort An, Tai Joon
collection PubMed
description 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.
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spelling pubmed-57717502018-01-21 Effects of Macrolide and Corticosteroid in Neutrophilic Asthma Mouse Model An, Tai Joon Rhee, Chin Kook Kim, Ji Hye Lee, Young Rong Chon, Jin Young Park, Chan Kwon Yoon, Hyoung Kyu Tuberc Respir Dis (Seoul) Original Article 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. The Korean Academy of Tuberculosis and Respiratory Diseases 2018-01 2017-12-21 /pmc/articles/PMC5771750/ /pubmed/29332324 http://dx.doi.org/10.4046/trd.2017.0108 Text en Copyright©2018. The Korean Academy of Tuberculosis and Respiratory Diseases http://creativecommons.org/licenses/by-nc/4.0/ It is identical to the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/)
spellingShingle Original Article
An, Tai Joon
Rhee, Chin Kook
Kim, Ji Hye
Lee, Young Rong
Chon, Jin Young
Park, Chan Kwon
Yoon, Hyoung Kyu
Effects of Macrolide and Corticosteroid in Neutrophilic Asthma Mouse Model
title Effects of Macrolide and Corticosteroid in Neutrophilic Asthma Mouse Model
title_full Effects of Macrolide and Corticosteroid in Neutrophilic Asthma Mouse Model
title_fullStr Effects of Macrolide and Corticosteroid in Neutrophilic Asthma Mouse Model
title_full_unstemmed Effects of Macrolide and Corticosteroid in Neutrophilic Asthma Mouse Model
title_short Effects of Macrolide and Corticosteroid in Neutrophilic Asthma Mouse Model
title_sort effects of macrolide and corticosteroid in neutrophilic asthma mouse model
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5771750/
https://www.ncbi.nlm.nih.gov/pubmed/29332324
http://dx.doi.org/10.4046/trd.2017.0108
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