Blockade of high mobility group box-1 protein attenuates experimental severe acute pancreatitis

AIM: To examine the effects of anti-high mobility group box 1 (HMGB1) neutralizing antibody in experimental severe acute pancreatitis (SAP). METHODS: SAP was induced by creating closed duodenal loop in C3H/HeN mice. SAP was induced immediately after intraperitoneal injection of anti-HMGB1 neutralizing antibody (200 mu g). Severity of pancreatitis, organ injury (liver, kidney and lung), and bacterial translocation to pancreas was examined 12 h after induction of SAP. RESULTS: Anti-HMGB1 neutralizing antibody significantly improved the elevation of the serum amylase level and the histological alterations of pancreas and lung in SAR Anti-HMGB1 antibody also significantly ameliorated the elevations of serum alanine aminotransferase and creatinine in SAR However, anti-HMGB1 antibody worsened the bacterial translocation to pancreas. CONCLUSION: Blockade of HMGB1 attenuated the development of SAP and associated organ dysfunction, suggesting that HMGB1 may act as a key mediator for inflammatory response and organ injury in SAP. (c) 2006 The WJG Press. All rights reserved.