Ascites of severe acute pancreatitis in rats transcriptionally up-regulates expression of interleukin-6 and-8 in vascular endothelium and mononuclearleukocytes

The molecular mechanisms that link acute pancreatitis and multiple organ fa ilure remain unknown. We examined the effect of ascitic fluids prepared fro m rats with experimental necrotizing pancreatitis on the expression of inte rleukin (IL) -6 and IL-8 in human umbilical vein endothelial cells (HUVEC) and human monocytic THP-1 cells. Incubation of HUVEC or THP-1 cells with th e ascitic fluids resulted in a concentration-dependent up-regulation of the cytokine expression with comparable mRNA induction. Electrophoretic mobili ty shift assay revealed that the ascitic fluids increased the nuclear facto r-kappa B (NF-kappa B) and NF-IL6 binding activities. Intraperitoneal injec tion of ascitic fluids into healthy rats induced the activation of NF-kappa B in the infiltrating leukocytes in the lung. Our results suggested that a scitic fluids may play a role in the pathophysiology of severe acute pancre atitis through the activation of transcription factors and consequent cytok ine productions in distant organs.