OBJECTIVES: Systemic inflammatory mediators, including the protein high-mobility group box 1 (HMGB1), play an important role in the development of acute pancreatitis. Anticoagulants, such as antithrombin III (AT III), inhibit inflammation resulting from various causes, but their mechanism of action is not well understood. Because acute pancreatitis is a severe inflammatory disease, we hypothesized that AT III would inhibit inflammation and prevent cerulein-induced acute pancreatitis. METHODS: Experimental animals received or were saline injected with a bolus of 250 IU/kg of AT III followed by intraperitoneal injections of 50 mg/kg of cerulein. Levels of cytokines (interleukin 6 and tumor necrosis factor alpha), nitric oxide (NO), and HMGB1 were measured in serum and pancreatic tissue at regular intervals for 12 hours after the cerulein injection. RESULTS: Pancreas histopathology and wet-dry ratio significantly improved in the AT III-injected (250 IU/kg) animals compared with the saline-injected rats. Serum and pancreas HMGB1 levels decreased over time in AT III-treated animals. Antithrombin III also decreased cytokine, NO, and HMGB1 levels during cerulein-induced inflammation. As a result, AT III ameliorated the pathologic pancreas in the rat model of cerulein-induced acute pancreatitis. CONCLUSIONS: Antithrombin III treatment inhibited the secretion of cytokines, NO, and HMGB1 and prevented cerulein-induced acute pancreatitis in the rat model.
OBJECTIVES: Systemic inflammatory mediators, including the protein high-mobility group box 1 (HMGB1), play an important role in the development of acute pancreatitis. Anticoagulants, such as antithrombin III (AT III), inhibit inflammation resulting from various causes, but their mechanism of action is not well understood. Because acute pancreatitis is a severe inflammatory disease, we hypothesized that AT III would inhibit inflammation and prevent cerulein-induced acute pancreatitis. METHODS: Experimental animals received or were saline injected with a bolus of 250 IU/kg of AT III followed by intraperitoneal injections of 50 mg/kg of cerulein. Levels of cytokines (interleukin 6 and tumor necrosis factor alpha), nitric oxide (NO), and HMGB1 were measured in serum and pancreatic tissue at regular intervals for 12 hours after the cerulein injection. RESULTS: Pancreas histopathology and wet-dry ratio significantly improved in the AT III-injected (250 IU/kg) animals compared with the saline-injected rats. Serum and pancreas HMGB1 levels decreased over time in AT III-treated animals. Antithrombin III also decreased cytokine, NO, and HMGB1 levels during cerulein-induced inflammation. As a result, AT III ameliorated the pathologic pancreas in the rat model of cerulein-induced acute pancreatitis. CONCLUSIONS:Antithrombin III treatment inhibited the secretion of cytokines, NO, and HMGB1 and prevented cerulein-induced acute pancreatitis in the rat model.