Endotoxin-induced translocation of interleukin-6 from lungs to the systemic circulation

Eiji Tamagawa, Koichi Suda, Yuan Wei, Li Xing, Tammy Mui, Yuexin Li, Stephan F. van Eeden, S. F.Paul Man, Don D. Sin

研究成果: Article査読

20 被引用数 (Scopus)

抄録

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 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.

本文言語English
ページ(範囲)251-258
ページ数8
ジャーナルInnate Immunity
15
4
DOI
出版ステータスPublished - 2009
外部発表はい

All Science Journal Classification (ASJC) codes

  • 微生物学
  • 免疫学
  • 分子生物学
  • 細胞生物学
  • 感染症

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