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Azithromycin inhibits neutrophil accumulation in airways by affecting interleukin- 17 downstream signals

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Author:
No author available
Journal Title:
Chinese Medical Journal
Issue:
3
DOI:
10.3760/cma.j.issn.0366-6999.2012.03.017
Key Word:
azithromycin;macrolides;neutrophils;interleukin-17

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 (mlL-17) stimulation.After the mlL-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 mlL-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.

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