Blockade of high mobility group box-1 protein attenuates experimental severe acute pancreatitis.
OBJECTIVE
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 microg). 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 SAP. Anti-HMGB1 antibody also significantly ameliorated the elevations of serum alanine aminotransferase and creatinine in SAP. However, anti-HMGB1 antibody worsened the bacterial translocation to pancreas.


CONCLUSIONS
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.
Sawa
Hidehiro
H
Department of Gastroenterological Surgery, Kobe University Graduate School of Medical Sciences, Kobe 650-0017, Japan. hdhrsawa@med.kobe-u.ac.jp
Ueda
Takashi
T
Takeyama
Yoshifumi
Y
Yasuda
Takeo
T
Shinzeki
Makoto
M
Nakajima
Takahiro
T
Kuroda
Yoshikazu
Y
D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D005260:Female; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors* / Q000276:immunology*; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D008809:Mice, Inbred C3H; D010195:Pancreatitis / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D012720:Severity of Illness Index
D000906:Antibodies; D024243:HMGB1 Protein