New Biomarkers in an Acute Model of Live Escherichia coli-induced Sepsis in Pigs

• Published in: Scandinavian journal of immunology Vol. 68; no. 1; pp. 75 - 84
• Main 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
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01-07-2008; Blackwell Publishing Ltd
• Subjects: Animals; Biomarkers - blood; Disease Models, Animal; Escherichia; Escherichia coli; Hemodynamics; Inflammation Mediators - blood; Interleukin-12 - blood; Matrix Metalloproteinase 9 - blood; Sepsis - blood; Sepsis - immunology; Sepsis - physiopathology; Swine
• ISSN: 0300-9475; 1365-3083
• DOI: 10.1111/j.1365-3083.2008.02122.x

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.