Interleukin-6 mediates pulmonary vascular permeability in a two-hit model of ventilator-associated lung injury.
Interleukin-6 mediates pulmonary vascular permeability in a two-hit model of ventilator-associated lung injury.
复制标题
DOI：
10.3109/01902148.2011.620680
复制
发表时间：
2011-12
影响因子：
1.7
通讯作者：
Becker PM
中科院分区：
文献类型：
--
作者：
Gurkan OU;He C;Zielinski R;Rabb H;King LS;Dodd-o JM;D'Alessio FR;Aggarwal N;Pearse D;Becker PM
为验证IL-6在呼吸机相关性肺损伤(VALI)发病机制中的作用，将IL-6基因缺陷(IL-6−/−)小鼠和野生型对照(WT)小鼠随机分为MV(MV+ITHCl)和自主通气组(ITHCl)。4h后，通过测定肺灌洗液蛋白浓度、细胞总数和分类计数、肺湿重/干重比、肺细胞死亡、组织学炎症评分(LIS)和髓过氧化物酶(MPO)浓度来评估肺损伤。测定肺灌洗液和匀浆中血管内皮生长因子(VEGF)的浓度，因为IL-6和Stretch都调节这一强大的通透性介质的表达。与对照组相比，IL 6−/−组小鼠肺泡屏障功能障碍和肺泡灌洗液中血管内皮生长因子水平的升高明显减弱，而肺组织中血管内皮生长因子浓度则显著升高。IL-6缺失对肺泡通透性和血管内皮生长因子浓度的影响是非炎症的，因为WT和IL-6−/−小鼠在IT HCl+MV后实质MPO浓度、LIS、灌洗液总细胞数和细胞分类计数没有差异。这些数据支持IL-6在这个两次打击模型中促进VALI的作用。干扰IL-6表达或信号转导的策略可能是限制MV对炎症肺损伤作用的重要治疗靶点。
To test the hypothesis that 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 MV (MV+IT HCl) or spontaneous ventilation (IT HCl). After 4 hr, 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 IT HCl+MV. 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.
登录
查看更多内容
影响因子：
6.9
作者：
Jafari, B;Ouyang, B;Quinn, DA
通讯作者：
Quinn, DA
影响因子：
20.3
作者：
Dankbar, B;Padró, T;Kienast, J
通讯作者：
Kienast, J
DOI：
10.1165/ajrcmb.22.6.3779
发表时间：
2000-06-01
影响因子：
6.4
作者：
Kaner, RJ;Ladetto, JV;Crystal, RG
通讯作者：
Crystal, RG
影响因子：
3.6
作者：
Feurino, Louis W.;Zhang, Yuqing;Li, Min
通讯作者：
Li, Min
影响因子：
4.4
作者：
Fielding, Ceri A.;McLoughlin, Rachel M.;Jenkins, Brendan J.
通讯作者：
Jenkins, Brendan J.