Actions of Cytokines in Caerulein-induced Acute Pancreatitis in Mice

The purpose of this study was to investigate the etiologic relationship between cytokines and the onset and progression of acute pancreatitis. Acute pancreatitis was induced in BALB / c mice by administering six intraperitoneal injections of caerulein, each 1 hour apart. Measurements of pancreatic weight, plasma amylase, histopathologic scores, pancreatic myeloperoxidase (MPO), DNA, and protein were determined at 6, 12, 18, 24, 72, and 120 h after the first injection, and the levels of pancreatic tumor necrosis factor ( TNF) - α and interleukin (IL) -1β were measured at 6, 12, and 18 h. Some mice were treated with FR167653, a potent suppressant of TNF- α and IL-1 β production, and measurements were taken 18 h after the first injection of caerulein to see if this drug could affect the progression of acute pancreatitis. Plasma amylase concentration was highest at 12 h. The histologic severity . and pancreatic MPO activity were highest at 18 h. Pancreatic TNF- α was highest at 6 h, and IL-1β was highest at 12 h. Pancreatic weight, relative to DNA content, was significantly increased at 24 h. Pancreatic protein levels, relative to DNA content, were significantly increased at 12 and 18 h. The plasma amylase concentration, pancreatic MPO activity, pancreatic histologic scores, and the protein levels relative to DNA content, were significantly lower at 18 h, in mice treated with FR167653. Preventive administration of FR167653 ameliorated the caerulein-induced acute pancreatitis. TNF- α and IL-1β seem to be crucial factors in the onset and progression of acute pancreatitis, and blockade of these cytokines may attenuate the severity of acute pancreatitis.