Induction of Procalcitonin and Proinflammatory Cytokines in an Anhepatic Baboon Endotoxin Shock Model

Abstract

Our objective was to evaluate the role of the liver for procalcitonin (PCT) and cytokine induction in a baboon endotoxin shock model. Complete liver resection with portocaval anastomosis was established in a baboon prior to the induction of endotoxin shock by intravenous administration of endotoxin (100 microg/kg LPS Escherichia coli). Two baboons without surgical intervention were used as controls. Plasma concentrations of PCT, tumor necrosis factor (TNF)-alpha, interleukin (IL) 6, IL-8, endotoxin, and hemodynamic and metabolic parameters were measured pre- and postoperatively and until 6 h after endotoxin administration. PCT concentrations increased to 1.2 and 4.6 ng/mL in control animals at 6 h, but remained below 0.3 ng/mL in the anhepatic baboon. IL-6 and IL-8 increased only for few hours in controls, but remained elevated in the hepatectomized animal near their maximum (IL-6, 2-6 ng/mL) or several-fold higher (IL-8, 30-35 ng/mL), whereas TNF-alpha response was only a small fraction (0.3 ng/mL) of the controls. Endotoxin was much higher and longer persisting in the hepatectomized animal compared with controls. The near absence of PCT production in the anhepatic baboon suggests a primary role for the liver as a source of PCT production during endotoxin shock. Furthermore, the liver also seems to be an important source of TNF-alpha, but not IL-6 or IL-8.