Kupffer cell blockade reduces hepatic and systemic cytokine levels and lung injury in hemorrhagic pancreatitis in rats

Severe acute pancreatitis (AP) is associated with both the local (pancreati c) release of cytokines and an elevation in their systemic plasma concentra tions. This may lead to organ dysfunction and death of the patient. The aim s of this study were to investigate the source(s) of systemic cytokine prod uction during experimental AP. Forty-two rats were allocated to five groups (control, sham operation and saline injection, sham operation and gadolini um chloride injection, intraductal sodium-taurocholate infusion and saline injection, or intraductal sodium-taurocholate infusion and gadolinium chlor ide injection). Blood from the iliac artery, portal vein, and hepatic vein, along with tissue from the pancreas, liver, and lung, were collected. Seru m levels of TNF alpha, IL-1 beta, IL-6, and IL-10 were determined by enzyme -linked immunosorbent assay. Tissue mRNA for IL-1 beta and IL-10 was assess ed by reverse-transcription polymerase chain reaction. In untreated animals with AP, the lowest serum cytokine levels were found in the portal vein. i n the hepatic vein, the levels of TNF alpha, IL-1 beta, and IL-6 were highe r. The highest serum levels were detected in the systemic circulation. In t he gadolinium chloride-treated group, there was no increase in hepatic or s ystemic cytokine levels and less lung injury was observed. Extrapancreatic cytokine production from both the liver and the lung contributed significan tly to systemic levels of TNF alpha, IL-1 beta, IL-6, and IL-10 in this exp erimental model of AP.