Anti‐High‐Mobility Group Box Chromosomal Protein 1 Antibodies Improve Survival of Rats with Sepsis

• DOI: 10.1007/s00268-005-0369-2
• Publication Date: 2006-07-18T12:48:49Z
• Authors: Koichi Suda; Yuko Kitagawa; Soji Ozawa; Yoshiro Saikawa; Masakazu Ueda; Masahito Ebina; Shingo Yamada; Satoru Hashimoto; Shinji Fukata; Edward Abraham; Ikuro Maruyama; Masaki Kitajima; Akitoshi Ishizaka
• Keywords: HMGB1; Cecum

AbstractBackgroundHigh‐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.MethodsAdult 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.ResultsTreatment 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.ConclusionsThe 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.