Systemic endotoxin, antiendotoxin antibodies and proinflammatory cytokines in the taurocholate model of acute pancreatitis

Background The endotoxin–proinflammatory cytokine cascade has been implicated in the systemic complications of severe acute pancreatitis. Although systemic proinflammatory cytokine activation has been demonstrated in experimental models, the initiating event may be pancreatic inflammation and not systemic endotoxaemia. The aim of this study was to characterise the systemic tumour necrosis factor (TNF) and interleukin-6 (IL-6) response in the taurocholate model of severe acute pancreatitis and to evaluate the role of endotoxaemia, by measuring endotoxin and antiendotoxin antibodies in the systemic compartment. Methods Acute pancreatitis was induced by the retrograde infusion of 0.2 ml 5% sodium taurocholate into the pancreas of male Wistar rats. Saline infusion was used in control rats. Animals were randomised to have venous blood sampling at 1, 2, 4, 6 or 12 h after pancreatic infusion. Blood samples were assayed for endotoxin [limulus amoebocyte lysate (LAL) assay], immunoglobulin(lg)G and IgM antiendotoxin antibodies (ELISA), TNF (WEHI bioassay and ELISA) and IL-6 (B9 bioassay). Results Plasma endotoxin was not detected and there was no difference in IgG and IgM antiendotoxin antibody concentration between pancreatitis animals and controls. At 1 and 2 h, systemic TNF was detected in rats with pancreatitis using both bioassay and ELISA, but not in controls ( p p p Conclusion Systemic proinflammatory cytokine activation occurs in the taurocholate model of severe acute panceatitis. TNF activation is biphasic, occurring at 1 and 2 h following induction of pancreatitis and again at 12 h, while systemic IL-6 concentration increased throughout the period of study. These cytokine responses may be independent of systemic endotoxaemia, since endotoxin was not detected in the systemic compartment and there was no change in the concentration of antiendotoxin antibodies.