To clarify the role of cytokines and acinar cell apoptosis in the pathogenesis of acute pancreatitis, we investigated the expression of intrapancreatic cytokines and apoptosis-related molecules in mice after pancratic duct ligation (PDL). From day 1 or 3 after PDL, the expression of interleukin-1alpha (IL-1alpha), IL-1beta, IL-1 receptor antagonist, IL-6, IL-10, and tumor necrosis factor (TNF-alpha) mRNA were up-regulated in the pancreas, suggesting that these cytokines may be involved in the development of pancreatitis after PDL. Acinar cell apoptosis was observed in the pancreas at rates of 0.13 +/- 0.03, 1.32 +/- 0.38, and 0.86 +/- 0.23% on days 1, 3, and 7 after PDL, respectively. Significant increases in intrapancreatic mRNA levels of TNF-alpha, Fas ligand (FasL), and IL-1beta-converting enzyme (ICE) were observed from day 3 after PDL with the appearance of acinar cell apoptosis. The serum amylase activity peaked on day 1 after PDL and gradually decreased on days 3 and 7 after PDL. These results suggest that acinar cell apoptosis induced after PDL may modulate the progression of acute pancreatitis by reducing the release of digestive enzymes and may therefore be a host defense mechanism, and that acinar cell apoptosis after PDL may be mediated by the TNF-alpha and/or Fas/FasL and ICE system.