title: Long-term azithromycin ameliorates not only airway inflammation but also remodeling in a murine model of chronic asthma.
abstract: OBJECTIVE
  We investigated the effect of long-term treatment with azithromycin on the pathogenesis of chronic asthma with airway remodeling.
  
  
  METHODS
  Six-week-old-BALB/c mice were sensitized with ovalbumin (OVA) combined with lipopolysaccharide (LPS) for 1 month, then challenged with OVA for 3 months. Azithromycin at 75 mg/kg was administered via oral gavage five times a week during the challenge period. Inflammatory cells, T helper 2 cytokines in bronchoalveolar lavage fluid (BAL) fluid, and airway hyperresponsiveness (AHR) were measured. Parameters related to airway remodeling were evaluated. The levels of neutrophil elastase, Interleukin (IL)-8, and BRP-39 (human homologue YKL-40) were assessed. The expression of MAPK and NF-κB signaling were investigated.
  
  
  RESULTS
  Long-term treatment with azithromycin improved AHR and airway inflammation compared with the OVA and the OVA/LPS groups. The concentrations of IL-5 and IL-13 in the OVA/LPS group decreased significantly after azithromycin administration. The levels of neutrophil elastase and IL-8, as surrogate markers of neutrophil activation, were reduced in the azithromycin group compared with the OVA/LPS group. Goblet cell hyperplasia and the smooth muscle thickening of airway remodeling were attenuated after azithromycin treatment. The expression of MAPK/NF-kappaB signal and the level of BRP-39 in the lung decreased remarkably in the OVA/LPS with azithromycin-treated group.
  
  
  CONCLUSIONS
  This study suggests that in a murine model of chronic asthma, long-term azithromycin treatment ameliorates not only airway inflammation but also airway remodeling by influencing on neutrophilc-related mediators, BRP-39 and MAPK/NF-κB signal pathways. Macrolide therapy might be an effective adjuvant therapy in a chronic, severe asthma with remodeling airway.
authors.affiliation: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kang
authors.affiliation: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Mi Ran
authors.initials: MR
authors.lastname: Jo
authors.affiliation: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Hyeon Hui
authors.initials: HH
authors.lastname: Kang
authors.affiliation: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Sung Kyoung
authors.initials: SK
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Myoung Sook
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Yong Hyun
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Seok Chan
authors.initials: SC
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Soon Seog
authors.initials: SS
authors.lastname: Kwon
authors.affiliation: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Sook Young
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address: medkjw@catholic.ac.kr.
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Kim
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D017963:Azithromycin / Q000627:therapeutic use*; D016535:Bronchial Hyperreactivity / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D005260:Female; D007378:Interleukins / Q000378:metabolism; D019272:Leukocyte Elastase / Q000378:metabolism; D008070:Lipopolysaccharides; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010047:Ovalbumin; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D007378:Interleukins; D008070:Lipopolysaccharides; D017963:Azithromycin; D010047:Ovalbumin; D020928:Mitogen-Activated Protein Kinases; D019272:Leukocyte Elastase
keywords: Airway remodeling; Asthma; Azithromycin; Macrolide