title: Azithromycin inhibits neutrophil accumulation in airways by affecting interleukin-17 downstream signals.
abstract: BACKGROUND
  Azithromycin can reduce neutrophil accumulation in neutrophilic pulmonary diseases. However, the precise mechanism behind this action remains unknown. Our experiment assessed whether azithromycin inhibits neutrophil accumulation in the airways by affecting interleukin-17 (IL-17) downstream signals.
  
  
  METHODS
  Mice were pretreated with azithromycin before murine IL-17A (mIL-17) stimulation. After the mIL-17 stimulation, the levels of six neutrophil-mobilizing cytokines were determined by enzyme-linked immunosorbent assay (ELISA) tests in bronchoalveolar lavage (BAL) fluid; IL-6, CXC chemokine ligand-1 (CXCL-1), CXCL-5, macrophage inflammatory protein-2 (MIP-2), granulocyte colony-stimulating factor (G-CSF), and granulocyte macrophage colony-stimulating factor (GM-CSF). The number of neutrophils in BAL fluid were evaluated by cytospin preparations.
  
  
  RESULTS
  (1) Azithromycin pretreatment significantly inhibited both the release of three neutrophil-mobilizing cytokines (MIP-2, CXCL-5 and GM-CSF) and the accumulation of neutrophils in airways caused by mIL-17 stimulation. (2) The levels of three neutrophil-mobilizing cytokines (IL-6, MIP-2 and GM-CSF) were positively correlated with the numbers of neutrophil in BAL fluid.
  
  
  CONCLUSIONS
  Azithromycin can inhibit neutrophil accumulation in the airways by affecting IL-17 downstream signals. This finding suggests that macrolide antibiotic application might be useful in prevention of neutrophilic pulmonary diseases characterized by high levels of IL-17.
authors.affiliation: Division of Respiratory Medicine, Department of Internal Medicine, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430073, China.
authors.forename: Nguyen Van
authors.initials: NV
authors.lastname: Luu
authors.forename: Jiong
authors.initials: J
authors.lastname: Yang
authors.forename: Xue-Ju
authors.initials: XJ
authors.lastname: Qu
authors.forename: Ming
authors.initials: M
authors.lastname: Guo
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Qiao-Yang
authors.initials: QY
authors.lastname: Xian
authors.forename: Zhi-Jiao
authors.initials: ZJ
authors.lastname: Tang
authors.forename: Zhi-Xiang
authors.initials: ZX
authors.lastname: Huang
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D017963:Azithromycin / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D054426:Chemokine CXCL2 / Q000378:metabolism; D019743:Chemokines, CXC / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D020381:Interleukin-17 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D054426:Chemokine CXCL2; D019743:Chemokines, CXC; D020381:Interleukin-17; D015850:Interleukin-6; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D017963:Azithromycin