Azithromycin attenuates effects of lipopolysaccharide on lung allograft bronchial epithelial cells

J Heart Lung Transplant. 2008 Nov;27(11):1210-6. doi: 10.1016/j.healun.2008.07.026. Epub 2008 Oct 1.


Background: The bronchial epithelium is a source of mediators that may play a role in the airway inflammation and remodeling of post-transplant obliterative bronchiolitis (OB). Traditional strategies have failed to have an impact on OB. Recent studies have suggested a role for azithromycin in managing the condition. In this study we aimed to determine the effect of azithromycin on LPS-mediated epithelial release of factors relevant to airway neutrophilia and remodeling in a unique population of primary bronchial epithelial cells (PBECs) derived from stable lung allografts.

Methods: PBECs were established from bronchial brushings of stable lung transplant recipients and treated with lipopolysaccharide (LPS, 0.1, 1 and 10 microg/ml) for 48 hours. Interleukin-8 (IL-8), granulocyte macrophage colony-stimulating factor (GM-CSF) and vascular endothelial growth factor (VEGF) protein levels were measured by Luminex analyzer. PBECs were then incubated with LPS and azithromycin, and protein levels were again determined.

Results: LPS caused a significant increase in IL-8 and GM-CSF at concentrations of 1 and 10 microg/ml, with no effect on VEGF release. Azithromycin caused a significant decrease in the LPS-stimulated IL-8 and GM-CSF release.

Conclusions: LPS upregulates release of IL-8 and GM-CSF from PBECs derived from stable lung allografts. Sub-microbicidal concentrations of azithromycin attenuate this and may, therefore, alleviate infection-driven neutrophilic airway inflammation and remodeling in the allograft airway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / therapeutic use
  • Azithromycin / therapeutic use*
  • Bronchi / drug effects
  • Bronchi / physiology
  • Bronchoalveolar Lavage Fluid
  • Bronchoscopy
  • Epithelial Cells / drug effects
  • Epithelial Cells / physiology
  • Granulocyte-Macrophage Colony-Stimulating Factor / blood
  • Humans
  • Inflammation / prevention & control
  • Interleukin-8 / blood
  • Lipopolysaccharides / pharmacology*
  • Lung Transplantation / physiology*
  • Transplantation, Homologous


  • Anti-Bacterial Agents
  • Interleukin-8
  • Lipopolysaccharides
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Azithromycin