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- Title
Endotoxin-induced translocation of interleukin-6 from lungs to the systemic circulation.
- Authors
Tamagawa, Eiji; Suda, Koichi; Yuan Wei; Li Xing; Mui, Tammy; Yuexin Li; van Eeden, Stephan F.; Man, S. F. Paul; Sin, Don D.
- Abstract
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 μg) and measured IL-6 in the serum and broncho-alveolar lavage (BAL) fluid (n=33 mice). We repeated the experiment following 3 d 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 3 d 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.
- Subjects
ENDOTOXINS; INTERLEUKIN-6; BRONCHOALVEOLAR lavage; BLOOD circulation; BLOOD plasma
- Publication
Innate Immunity, 2009, Vol 15, Issue 4, p251
- ISSN
1753-4259
- Publication type
Article
- DOI
10.1177/1753425909104782