title: Interleukin-6 mediates pulmonary vascular permeability in a two-hit model of ventilator-associated lung injury.
abstract: To test the hypothesis that interleukin-6 (IL-6) contributes to the development of ventilator-associated lung injury (VALI), IL-6-deficient (IL6(-/-)) and wild-type control (WT) mice received intratracheal hydrochloric acid followed by randomization to mechanical ventilation (MV + IT HCl) or spontaneous ventilation (IT HCl). After 4 hours, injury was assessed by estimation of lung lavage protein concentration and total and differential cell counts, wet/dry lung weight ratio, pulmonary cell death, histologic inflammation score (LIS), and parenchymal myeloperoxidase (MPO) concentration. Vascular endothelial growth factor (VEGF) concentration was measured in lung lavage and homogenate, as IL-6 and stretch both regulate expression of this potent mediator of permeability. MV-induced increases in alveolar barrier dysfunction and lavage VEGF were attenuated in IL6(-/-) mice as compared with WT controls, whereas tissue VEGF concentration increased. The effects of IL-6 deletion on alveolar permeability and VEGF concentration were inflammation independent, as parenchymal MPO concentration, LIS, and lavage total and differential cell counts did not differ between WT and IL6(-/-) mice following MV + IT HCl. These data support a role for IL-6 in promoting VALI in this two-hit model. Strategies to interfere with IL-6 expression or signaling may represent important therapeutic targets to limit the injurious effects of MV in inflamed lungs.
authors: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Ozlem U
authors: OU
authors: Gurkan
authors: Chaoxia
authors: C
authors: He
authors: Rachel
authors: R
authors: Zielinski
authors: Hamid
authors: H
authors: Rabb
authors: Landon S
authors: LS
authors: King
authors: Jeffrey M
authors: JM
authors: Dodd-o
authors: Franco R
authors: FR
authors: D'Alessio
authors: Neil
authors: N
authors: Aggarwal
authors: David
authors: D
authors: Pearse
authors: Patrice M
authors: PM
authors: Becker
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002199:Capillary Permeability / Q000502:physiology*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D055370:Lung Injury / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011897:Random Allocation; D012121:Respiration, Artificial / Q000379:methods; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D012122:Ventilators, Mechanical
chemical_list: D015850:Interleukin-6; D042461:Vascular Endothelial Growth Factor A