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

Research output: Contribution to journalArticle

18 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Endotoxins
Interleukin-6
Lung
Cytokines
Serum
Dexamethasone
Therapeutic Irrigation
Bronchoalveolar Lavage Fluid
Heart Atria
Aorta
Animal Models
Inflammation
Infection
Therapeutics

Keywords

  • Endotoxin
  • Interleukin-6
  • Systemic Inflammation
  • Translocation

ASJC Scopus subject areas

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

Cite this

Tamagawa, E., Suda, K., Wei, Y., Xing, L., Mui, T., Li, Y., ... 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

Endotoxin-induced translocation of interleukin-6 from lungs to the systemic circulation. / Tamagawa, Eiji; Suda, Koichi; Wei, Yuan; Xing, Li; Mui, Tammy; Li, Yuexin; van Eeden, Stephan F.; Man, S. F Paul; Sin, Don D.

In: Innate Immunity, Vol. 15, No. 4, 2009, p. 251-258.

Research output: Contribution to journalArticle

Tamagawa, E, Suda, K, Wei, Y, Xing, L, Mui, T, Li, Y, van Eeden, SF, Man, SFP & Sin, DD 2009, 'Endotoxin-induced translocation of interleukin-6 from lungs to the systemic circulation', Innate Immunity, vol. 15, no. 4, pp. 251-258. https://doi.org/10.1177/1753425909104782
Tamagawa, Eiji ; Suda, Koichi ; Wei, Yuan ; Xing, Li ; Mui, Tammy ; Li, Yuexin ; van Eeden, Stephan F. ; Man, S. F Paul ; Sin, Don D. / Endotoxin-induced translocation of interleukin-6 from lungs to the systemic circulation. In: Innate Immunity. 2009 ; Vol. 15, No. 4. pp. 251-258.
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