Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
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Effects of Macrolide and Corticosteroid in Neutrophilic Asthma Mouse Model

  • An, Tai Joon (Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Rhee, Chin Kook (Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Kim, Ji Hye (Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Lee, Young Rong (Department of Anesthesiology and Pain Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Chon, Jin Young (Department of Anesthesiology and Pain Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Park, Chan Kwon (Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Yoon, Hyoung Kyu (Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea)
  • Received : 2017.09.06
  • Accepted : 2017.11.21
  • Published : 2018.01.31
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Abstract

Background: Asthma is a disease of chronic airway inflammation with heterogeneous features. Neutrophilic asthma is corticosteroid-insensitive asthma related to absence or suppression of $T_H2$ process and increased $T_H1$ and/or $T_H17$ 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 ${\gamma}$, and tumor necrosis factor ${\alpha}$ 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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References

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