title: Clarithromycin ameliorates pulmonary inflammation induced by short term cigarette smoke exposure in mice.
abstract: BACKGROUND
  Cigarette smoking is considered to be one of major causes of acute worsening of asthma as well as chronic obstructive pulmonary disease (COPD). Macrolide antibiotics have been reported to reduce the risk of exacerbations of COPD, and possibly neutrophilic asthma. However, the effect of clarithromycin (CAM) on pulmonary inflammation caused by short term exposure to cigarette smoke still remains to be investigated.
  
  
  METHODS
  C57BL/6J female mice were daily exposed to tobacco smoke using a tobacco smoke exposure system, or clean air for 8 days, while simultaneously treated with either oral CAM or vehicles. Twenty four hours after the last exposure, mice were anaesthetized and sacrificed, and bronchoalveolar lavage (BAL) fluids were collected. Cellular responses in BAL fluids were evaluated. Levels of cytokine mRNA in the lung tissues were measured by quantitative RT-PCR. Paraffin-embedded lung tissues were evaluated to quantitate degree of neutrophil infiltration.
  
  
  RESULTS
  The numbers of total cells, macrophages and neutrophils in the BAL fluid of smoke-exposed mice were significantly increased as compared to clean air group. These changes were significantly ameliorated in CAM-treated mice. The lung morphological analysis confirmed decrease of neutrophils by CAM treatment. Studies by quantitative PCR demonstrated CAM treatment significantly reduced lung expression levels of IL-17A, keratinocyte-derived chemokine (KC), granulocyte-macrophage colony stimulating factor (GM-CSF) and MMP-9 induced by cigarette smoke.
  
  
  CONCLUSIONS
  We demonstrate that CAM administration resolves enhanced pulmonary inflammation induced by short term cigarette smoke exposure in mice.
authors.affiliation: Department of Respiratory Medicine, Kyorin University School of Medicine, Mitaka, Japan.
authors.forename: Masuo
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Respiratory Medicine, Kyorin University School of Medicine, Mitaka, Japan.
authors.forename: Hiroo
authors.initials: H
authors.lastname: Wada
authors.affiliation: Department of Respiratory Medicine, Kyorin University School of Medicine, Mitaka, Japan.
authors.forename: Kojiro
authors.initials: K
authors.lastname: Honda
authors.affiliation: Department of Respiratory Medicine, Kyorin University School of Medicine, Mitaka, Japan.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Nakamoto
authors.affiliation: Department of Respiratory Medicine, Kyorin University School of Medicine, Mitaka, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Inui
authors.affiliation: Department of Respiratory Medicine, Kyorin University School of Medicine, Mitaka, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Sada
authors.affiliation: Department of Respiratory Medicine, Kyorin University School of Medicine, Mitaka, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Respiratory Medicine, Kyorin University School of Medicine, Mitaka, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Takata
authors.affiliation: Department of Respiratory Medicine, Kyorin University School of Medicine, Mitaka, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Yokoyama
authors.affiliation: Department of Respiratory Medicine, Kyorin University School of Medicine, Mitaka, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Saraya
authors.affiliation: Department of Respiratory Medicine, Kyorin University School of Medicine, Mitaka, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kurai
authors.affiliation: Department of Respiratory Medicine, Kyorin University School of Medicine, Mitaka, Japan.
authors.forename: Haruyuki
authors.initials: H
authors.lastname: Ishii
authors.affiliation: Department of Respiratory Medicine, Kyorin University School of Medicine, Mitaka, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Goto
authors.affiliation: Department of Pathology, Kyorin University School of Medicine, Mitaka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kamma
authors.affiliation: Department of Respiratory Medicine, Kyorin University School of Medicine, Mitaka, Japan. Electronic address: htakizawa.alg@gmail.com.
authors.forename: Hajime
authors.initials: H
authors.lastname: Takizawa
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D017291:Clarithromycin / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D012906:Smoke; D062789:Tobacco Products
chemical_list: D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D012906:Smoke; D017291:Clarithromycin
keywords: Clarithromycin (PubChem CID: 84029); Cytokine; Macrolide; Neutrophil; Smoking