Azithromycin attenuates effects of lipopolysaccharide on lung allograft bronchial epithelial cells.
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.
Murphy
Desmond M
DM
Applied Immunobiology and Transplantation Research Group, Institute of Cellular Medicine, University of Newcastle upon Tyne, Newcastle upon Tyne, UK.
Forrest
Ian A
IA
Corris
Paul A
PA
Johnson
Gail E
GE
Small
Therese
T
Jones
Debbie
D
Fisher
Andrew J
AJ
Egan
Jim J
JJ
Cawston
Timothy E
TE
Lordan
James L
JL
Ward
Chris
C
D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D017963:Azithromycin / Q000627:therapeutic use*; D001980:Bronchi / Q000187:drug effects / Q000502:physiology; D001992:Bronchoalveolar Lavage Fluid; D001999:Bronchoscopy; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D016209:Interleukin-8 / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016040:Lung Transplantation / Q000502:physiology*; D014184:Transplantation, Homologous
D000900:Anti-Bacterial Agents; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D017963:Azithromycin