期刊
INNATE IMMUNITY
卷 15, 期 4, 页码 251-258出版社
SAGE PUBLICATIONS LTD
DOI: 10.1177/1753425909104782
关键词
Endotoxin; interleukin-6; translocation; systemic inflammation
资金
- Canada Research Chair
- BC Lung Association, AstraZeneca, Canada
- Michael Smith Foundation for Health Research
It is widely postulated that systemic inflammation related to lung infections is largely caused by cytokine translocation from the lungs into the systemic circulation but there is a paucity of animal models to evaluate this hypothesis. In this proof-of-concept study, we developed a murine model to determine whether interleukin (IL)-6, a primary inflammatory cytokine, translocates following airway exposure to endotoxin. We collected central venous blood from the right atrium and arterial blood from the aorta simultaneously at 4 h and 24 h following intratracheal exposure to endotoxin (25 mg) and measured IL-6 in the serum and broncho-alveolar lavage (BAL) fluid (n = 33 mice). We repeated the experiment following 3d of treatment with dexamethasone (n = 31 mice). Without stimulation, there was no significant arteriovenous gradient (3 pg/ml with interquartile range [IQR] of 3-5 pg/ml in arterial versus 18 pg/ml with IQR of 8-24 pg/ml in venous serum; P = 0.86). A significant arteriovenous difference was observed by 4 h post-exposure to endotoxin (2813 pg/ml with IQR of 1578-4316 pg/ml in arterial versus 1282 pg/ml with IQR of 778-2699 pg/ml in venous serum; P < 0.0001). The rise in the BAL IL-6 levels correlated with the increases in the arterial serum levels (P < 0.0001). Administration of intraperitoneal dexamethasone for 3d attenuated the increased arteriovenous gradient. This murine model facilitates the estimation of cytokine translocation across the lungs and evaluation of compounds to modulate this gradient.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据