TY - JOUR
T1 - Anti-high-mobility group box chromosomal protein 1 antibodies improve survival of rats with sepsis
AU - Suda, Koichi
AU - Kitagawa, Yuko
AU - Ozawa, Soji
AU - Saikawa, Yoshiro
AU - Ueda, Masakazu
AU - Ebina, Masahito
AU - Yamada, Shingo
AU - Hashimoto, Satoru
AU - Fukata, Shinji
AU - Abraham, Edward
AU - Maruyama, Ikuro
AU - Kitajima, Masaki
AU - Ishizaka, Akitoshi
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2006/9
Y1 - 2006/9
N2 - Background: High-mobility group box chromosomal protein 1 (HMGB1) has recently been shown to be an important late mediator of endotoxin shock, intraabdominal sepsis, and acute lung injury, and a promising therapeutic target of severe sepsis. We sought to investigate the effect of antibodies to HMGB1 on severe sepsis in a rat cecal ligation and puncture (CLP) model. Methods: Adult male Sprague-Dawley rats underwent CLP and then were randomly divided into two groups: treatment with anti-HMGB1 polyclonal antibodies, and non-immune IgG-treated controls. The serum HMGB1 concentrations were measured at ten time points (preoperatively, and postoperatively at 4, 8, 20, 32, and 48 h and at 3, 4, 5, and 6 days). Hematoxylin-eosin staining, elastica-Masson staining, and immunohistochemical staining for HMGB1 were performed on the cecum and the lung to assess pathological changes 24 h after the CLP procedure. Results: Treatment with anti-HMGB1 antibodies significantly increased survival [55% (anti-HMGB1) vs. 9% (controls); P< 0.01]. The serum HMGB1 concentrations at postoperative hours 20 and 32 of the anti-HMGB1 antibody-treated animals were significantly lower than those of the controls (P < 0.05). Treatment with anti-HMGB1 antibodies markedly diminished the pathological changes and the number of HMGB1-positive cells in the cecum and the lung. Conclusions: The present study demonstrates that anti-HMGB1 antibodies are effective in the treatment of severe sepsis in a rat model, thereby supporting the relevance of HMGB1 eradication therapy for severe sepsis.
AB - Background: High-mobility group box chromosomal protein 1 (HMGB1) has recently been shown to be an important late mediator of endotoxin shock, intraabdominal sepsis, and acute lung injury, and a promising therapeutic target of severe sepsis. We sought to investigate the effect of antibodies to HMGB1 on severe sepsis in a rat cecal ligation and puncture (CLP) model. Methods: Adult male Sprague-Dawley rats underwent CLP and then were randomly divided into two groups: treatment with anti-HMGB1 polyclonal antibodies, and non-immune IgG-treated controls. The serum HMGB1 concentrations were measured at ten time points (preoperatively, and postoperatively at 4, 8, 20, 32, and 48 h and at 3, 4, 5, and 6 days). Hematoxylin-eosin staining, elastica-Masson staining, and immunohistochemical staining for HMGB1 were performed on the cecum and the lung to assess pathological changes 24 h after the CLP procedure. Results: Treatment with anti-HMGB1 antibodies significantly increased survival [55% (anti-HMGB1) vs. 9% (controls); P< 0.01]. The serum HMGB1 concentrations at postoperative hours 20 and 32 of the anti-HMGB1 antibody-treated animals were significantly lower than those of the controls (P < 0.05). Treatment with anti-HMGB1 antibodies markedly diminished the pathological changes and the number of HMGB1-positive cells in the cecum and the lung. Conclusions: The present study demonstrates that anti-HMGB1 antibodies are effective in the treatment of severe sepsis in a rat model, thereby supporting the relevance of HMGB1 eradication therapy for severe sepsis.
UR - http://www.scopus.com/inward/record.url?scp=33748760336&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33748760336&partnerID=8YFLogxK
U2 - 10.1007/s00268-005-0369-2
DO - 10.1007/s00268-005-0369-2
M3 - Article
C2 - 16850155
AN - SCOPUS:33748760336
SN - 0364-2313
VL - 30
SP - 1755
EP - 1762
JO - World Journal of Surgery
JF - World Journal of Surgery
IS - 9
ER -