PMID- 16850155
OWN - NLM
STAT- MEDLINE
DCOM- 20061212
LR  - 20181113
IS  - 0364-2313 (Print)
IS  - 0364-2313 (Linking)
VI  - 30
IP  - 9
DP  - 2006 Sep
TI  - Anti-high-mobility group box chromosomal protein 1 antibodies improve survival of 
      rats with sepsis.
PG  - 1755-62
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.
FAU - Suda, Koichi
AU  - Suda K
AD  - Department of Surgery, School of Medicine, Keio University, Shinanomachi 35, 
      Shinjuku-ku, Tokyo 160-8582, Japan.
FAU - Kitagawa, Yuko
AU  - Kitagawa Y
FAU - Ozawa, Soji
AU  - Ozawa S
FAU - Saikawa, Yoshiro
AU  - Saikawa Y
FAU - Ueda, Masakazu
AU  - Ueda M
FAU - Ebina, Masahito
AU  - Ebina M
FAU - Yamada, Shingo
AU  - Yamada S
FAU - Hashimoto, Satoru
AU  - Hashimoto S
FAU - Fukata, Shinji
AU  - Fukata S
FAU - Abraham, Edward
AU  - Abraham E
FAU - Maruyama, Ikuro
AU  - Maruyama I
FAU - Kitajima, Masaki
AU  - Kitajima M
FAU - Ishizaka, Akitoshi
AU  - Ishizaka A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - World J Surg
JT  - World journal of surgery
JID - 7704052
RN  - 0 (Antibodies)
RN  - 0 (HMGB1 Protein)
RN  - 0 (Hbp1 protein, rat)
RN  - 0 (High Mobility Group Proteins)
RN  - 0 (Repressor Proteins)
SB  - IM
MH  - Animals
MH  - Antibodies/*therapeutic use
MH  - Cecum/pathology/surgery
MH  - Disease Models, Animal
MH  - HMGB1 Protein
MH  - High Mobility Group Proteins/blood/*immunology
MH  - Immunohistochemistry
MH  - Ligation
MH  - Male
MH  - Neutralization Tests
MH  - Peritonitis/*immunology/*therapy
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Repressor Proteins/blood/*immunology
MH  - Sepsis/*therapy
EDAT- 2006/07/20 09:00
MHDA- 2006/12/13 09:00
CRDT- 2006/07/20 09:00
PHST- 2006/07/20 09:00 [pubmed]
PHST- 2006/12/13 09:00 [medline]
PHST- 2006/07/20 09:00 [entrez]
AID - 10.1007/s00268-005-0369-2 [doi]
PST - ppublish
SO  - World J Surg. 2006 Sep;30(9):1755-62. doi: 10.1007/s00268-005-0369-2.