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

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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 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.

Original languageEnglish
Pages (from-to)251-258
Number of pages8
JournalInnate Immunity
Volume15
Issue number4
DOIs
Publication statusPublished - 2009

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Molecular Biology
  • Cell Biology
  • Infectious Diseases

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    Tamagawa, E., Suda, K., Wei, Y., Xing, L., Mui, T., Li, Y., van Eeden, S. F., Man, S. F. P., & Sin, D. D. (2009). Endotoxin-induced translocation of interleukin-6 from lungs to the systemic circulation. Innate Immunity, 15(4), 251-258. https://doi.org/10.1177/1753425909104782