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- Title
New Biomarkers in an Acute Model of Live Escherichia coli-induced Sepsis in Pigs.
- Authors
Castellheim, A.; Thorgersen, E. B.; Hellerud, B. C.; Pharo, A.; Johansen, H. T.; Brosstad, F.; Gaustad, P.; Brun, H.; Fosse, E.; Tønnessen, T. I.; Nielsen, E. W.; Mollnes, T. E.
- Abstract
We developed a live Escherichia coli model of acute sepsis in pigs with emphasize on biomarkers reflecting the early inflammatory response of sepsis. Healthy pigs, 25–35 kg, were challenged intravenously (IV) ( n = 12) or intrapulmonary ( n = 6) with live E. coli and observed for 3 and 5 h respectively. Control pigs received culture medium ( n = 6 + 3). Haemodynamic parameters and a broad panel of inflammatory mediators were measured. The dose of bacteria was carefully titrated to obtain a condition resembling the early phase of human septic shock. The IV group displayed a pro-inflammatory response [significant increase in tumour necrosis factor-α, interleukin (IL)-6 and IL-8] and an early anti-inflammatory response (significant increase in IL-10). For the first time, we demonstrate a significant increase in IL-12 and matrix metalloproteinase-9 (MMP) early in pig sepsis. Coagulation was activated (significant increase in thrombin–antithrombin complexes) and there was a significant decrease in the serum proteins suggesting capillary leakage. Haemodynamic parameters reflected a septic condition with significant decrease in systemic blood pressure, increases in heart rate, pulmonary artery pressure and base deficit. None of these changes was observed in the control group. Interleukin-1β and vascular endothelial growth factor increased in both groups. Nitric oxide measurements suggested an initial pulmonary vascular endothelial inflammatory response. The intrapulmonary group, which did not resemble septic condition, showed a substantial increase in MMP-9. In this porcine model of sepsis, IL-12 and MMP-9 were detected for the first time. These biomarkers may have an impact in the understanding and future treatment of sepsis.
- Subjects
BIOMARKERS; BIOINDICATORS; BIOCHEMISTRY; SEPSIS; BLOOD diseases; COMMUNICABLE diseases
- Publication
Scandinavian Journal of Immunology, 2008, Vol 68, Issue 1, p75
- ISSN
0300-9475
- Publication type
Article
- DOI
10.1111/j.1365-3083.2008.02122.x