Abstract
Background: Death in the early stages of severe acute pancreatitis is frequently the result of multiple organ dysfunction, but its mechanism is not clear. Aims: To investigate the state of nuclear factor-kappaB (NF-kappaB) in macrophages of rats with lethal pancreatitis, and to assess the effectiveness of pyrrolidine dithiocarbamate, an inhibitor of NF-kappaB, on the pathology and mortality. Methods: Taurocholate pancreatitis was produced in rats, and the severity of the disease, the mortality, and activation of NF-kappaB in peritoneal and alveolar macrophages were compared in rats receiving pyrrolidine dithiocarbamate (PDTC) treatment and those that were not. Results: Taurocholate pancreatitis produced massive necrosis, haemorrhage, and severe leucocyte infiltration in the pancreas as well as alveolar septal thickening in the lung. NF-kappaB was activated in peritoneal and alveolar macrophages six hours after pancreatitis induction. Pretreatment with PDTC dose-dependently attenuated the NF-kappaB activation and improved the survival of the rats, although it did not affect the early increase in serum amylase and histological findings. Conclusions: Early blockage of NF-kappaB activation may be effective in reducing fatal outcome in severe acute pancreatitis.