Title |
Anti-HMGB1 Neutralizing Antibody Ameliorates Gut Barrier Dysfunction and Improves Survival after Hemorrhagic Shock
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Published in |
Molecular Medicine, May 2006
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DOI | 10.2119/2006-00010.yang |
Pubmed ID | |
Authors |
Runkuan Yang, Tomoyuki Harada, Kevin P. Mollen, Jose M. Prince, Ryan M. Levy, Joshua A. Englert, Margot Gallowitsch-Puerta, LiHong Yang, Huan Yang, Kevin J. Tracey, Brian G. Harbrecht, Timothy R. Billiar, Mitchell P. Fink |
Abstract |
Intestinal barrier dysfunction occurs following hemorrhagic shock and resuscitation (HS/R). High-mobility group B1 (HMGB1) has been shown to increase the permeability of Caco-2 human enterocyte-like epithelial monolayers in vitro. In this study, we found that serum concentrations of HMGB1 were higher in blood samples obtained from 25 trauma victims with hemorrhagic shock than in 9 normal volunteers. We also studied whether treatment with anti-HMGB1 antibody can ameliorate HS/R-induced gut barrier dysfunction in mice. Animals were shocked by withdrawal of blood to maintain mean arterial pressure at 25 to 30 mmHg for 2 h. After resuscitation with shed blood plus Ringer's lactate solution, the mice were treated with either anti-HMGB1 antibody or nonimmune rabbit IgG. Serum HMGB1 concentrations were significantly higher in trauma victims than control mice. Treatment with anti-HMGB1 antibody improved survival at 24 h and ameliorated the development of ileal mucosal hyperpermeability to FITC-labeled dextran. At 24 h after HS/R, treatment with anti-HMGB1 antibody decreased bacterial translocation to mesenteric lymph nodes and was associated with lower circulating concentrations of IL-6 and IL-10. These data support the notion that HMGB1 is a mediator of HS/R-induced gut barrier dysfunction and suggest that anti-HMGB1 antibodies warrant further evaluation as a therapeutic to ameliorate the morbidity of HS/R in trauma patients. |
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United States | 1 | 100% |
Demographic breakdown
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United Kingdom | 2 | 3% |
Japan | 1 | 1% |
United States | 1 | 1% |
Unknown | 63 | 94% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 11 | 16% |
Student > Ph. D. Student | 10 | 15% |
Student > Doctoral Student | 7 | 10% |
Student > Bachelor | 5 | 7% |
Other | 4 | 6% |
Other | 16 | 24% |
Unknown | 14 | 21% |
Readers by discipline | Count | As % |
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Agricultural and Biological Sciences | 13 | 19% |
Biochemistry, Genetics and Molecular Biology | 6 | 9% |
Immunology and Microbiology | 3 | 4% |
Psychology | 2 | 3% |
Other | 9 | 13% |
Unknown | 15 | 22% |