Inhibition of nuclear factor-kappa B activation improves the survival of rats with taurocholate pancreatitis

Background-Death in the early stages of severe acute pancreatitis is freque ntly the result of multiple organ dysfunction, but its mechanism is not cle ar. Aims-To investigate the state of nuclear factor-kappa B (NF-kappa B) in mac rophages of rats with lethal pancreatitis, and to assess the effectiveness of pyrrolidine dithiocarbamate, an inhibitor of NF-kappa B, on the patholog y and mortality. Methods-Taurocholate pancreatitis was produced in rats, and the severity of the disease, the mortality, and activation of NF-kappa B in peritoneal and alveolar macrophages were compared in rats receiving pyrrolidine dithiocar bamate (PDTC) treatment and those that were not. Results-Taurocholate pancreatitis produced massive necrosis, haemorrhage, a nd severe leucocyte infiltration in the pancreas as well as alveolar septal thickening in the lung. NF-kappa B was activated in peritoneal and alveola r macrophages six hours after pancreatitis induction. Pretreatment with PDT C dose-dependently attenuated the NF-kappa B activation and improved the su rvival of the rats, although it did not affect the early increase in serum amylase and histological findings. Conclusions-Early blockage of NF-kappa B activation may be effective in red ucing fatal outcome in severe acute pancreatitis.