title: Clarithromycin and dexamethasone show similar anti-inflammatory effects on distinct phenotypic chronic rhinosinusitis: an explant model study.
abstract: BACKGROUND
  Phenotype of chronic rhinosinusitis (CRS) may be an important determining factor of the efficacy of anti-inflammatory treatments. Although both glucocorticoids and macrolide antibiotics have been recommended for the treatment of CRS, whether they have different anti-inflammatory functions for distinct phenotypic CRS has not been completely understood. The aim of this study is to compare the anti-inflammatory effects of clarithromycin and dexamethasone on sinonasal mucosal explants from different phenotypic CRS ex vivo.
  
  
  METHODS
  Ethmoid mucosal tissues from CRSsNP patients (n = 15), and polyp tissues from eosinophilic (n = 13) and non-eosinophilic (n = 12) CRSwNP patients were cultured in an ex vivo explant model with or without dexamethasone or clarithromycin treatment for 24 h. After culture, the production and/or expression of anti-inflammatory molecules, epithelial-derived cytokines, pro-inflammatory cytokines, T helper (Th)1, Th2 and Th17 cytokines, chemokines, dendritic cell relevant markers, pattern recognition receptors (PRRs), and tissue remodeling factors were detected in tissue explants or culture supernatants by RT-PCR or ELISA, respectively.
  
  
  RESULTS
  We found that both clarithromycin and dexamethasone up-regulated the production of anti-inflammatory mediators (Clara cell 10-kDa protein and interleukin (IL)-10), whereas down-regulated the production of Th2 response and eosinophilia promoting molecules (thymic stromal lymphopoietin, IL-25, IL-33, CD80, CD86, OX40 ligand, programmed cell death ligand 1, CCL17, CCL22, CCL11, CCL5, IL-5, IL-13, and eosinophilic cationic protein) and Th1 response and neutrophilia promoting molecules (CXCL8, CXCL5, CXCL10, CXCL9, interferon-γ, and IL-12), from sinonasal mucosa from distinct phenotypic CRS. In contrast, they had no effect on IL-17A production. The expression of PRRs (Toll-like receptors and melanoma differentiation-associated gene 5) was induced, and the production of tissue remodeling factors (transforming growth factor-β1, epidermal growth factor, basic fibroblast growth factor, platelet derived growth factor, vascular endothelial growth factor, and matrix metalloproteinase 9) was suppressed, in different phenotypic CRS by dexamethasone and clarithromycin in comparable extent.
  
  
  CONCLUSIONS
  Out of our expectation, our explant model study discovered herein that glucocorticoids and macrolides likely exerted similar regulatory actions on CRS and most of their effects did not vary by the phenotypes of CRS.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College; Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, People's Republic of China. zmsx77@163.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Zeng
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College; Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, People's Republic of China. otoris@126.com.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Li
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College; Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, People's Republic of China. majin75812@126.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College; Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, People's Republic of China. caoping2009@hotmail.com.
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: Cao
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College; Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, People's Republic of China. martin_wangheng@hotmail.com.
authors.forename: Heng
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College; Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, People's Republic of China. yhcui@tjh.tjmu.edu.cn.
authors.forename: Yong-Hua
authors.initials: YH
authors.lastname: Cui
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College; Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, People's Republic of China. zhengliuent@hotmail.com.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002908:Chronic Disease; D017291:Clarithromycin / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015735:Mifepristone / Q000494:pharmacology; D008954:Models, Biological; D010641:Phenotype; D010865:Pilot Projects; D051192:Receptors, Pattern Recognition / Q000378:metabolism; D012220:Rhinitis / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D012852:Sinusitis / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D051192:Receptors, Pattern Recognition; D015735:Mifepristone; D003907:Dexamethasone; D017291:Clarithromycin