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

The molecular mechanisms that link acute pancreatitis and multiple organ failure remain unknown. We examined the effect of ascitic fluids prepared from rats with experimental necrotizing pancreatitis on the expression of interleukin (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 the ascitic fluids resulted in a concentration-dependent up-regulation of the cytokine expression with comparable mRNA induction. Electrophoretic mobility shift assay revealed that the ascitic fluids increased the nuclear factor-kappa B (NF-kappa B) and NF-IL6 binding activities. Intraperitoneal injection of ascitic fluids into healthy rats induced the activation of NF-kappa B in the infiltrating leukocytes in the lung. Our results suggested that ascitic fluids may play a role in the pathophysiology of severe acute pancreatitis through the activation of transcription factors and consequent cytokine productions in distant organs.