Endotoxin-induced translocation of interleukin-6 from lungs to the systemic circulation
Autor: | Eiji Tamagawa, Stephan F. van Eeden, Koichi Suda, Don D. Sin, S. F. Paul Man, Yuan Wei, Li Xing, Yuexin Li, Tammy Mui |
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Rok vydání: | 2009 |
Předmět: |
Male
medicine.medical_specialty Pathology Immunology Anti-Inflammatory Agents Systemic inflammation Microbiology Dexamethasone Mice Internal medicine medicine.artery Intubation Intratracheal medicine Animals Interleukin 6 Lung Molecular Biology Aorta biology Interleukin-6 business.industry Interleukin Pneumonia Cell Biology Venous blood Endotoxins Mice Inbred C57BL Disease Models Animal Infectious Diseases medicine.anatomical_structure Endocrinology Blood Circulation biology.protein Arterial blood medicine.symptom business Bronchoalveolar Lavage Fluid medicine.drug |
Zdroj: | Innate Immunity. 15:251-258 |
ISSN: | 1753-4267 1753-4259 |
DOI: | 10.1177/1753425909104782 |
Popis: | 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; P50.0001). The rise in the BAL IL-6 levels correlated with the increases in the arterial serum levels (P50.0001). 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. |
Databáze: | OpenAIRE |
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