title: High-dose immunoglobulin preparations improve survival in a CLP-induced rat model of sepsis.
abstract: OBJECTIVE
  The efficacy of intravenous immunoglobulin G in the treatment of patients with severe sepsis or septic shock is still being debated. We investigated the impact of high-dose immunoglobulin administration on the survival rate and serum high-mobility group box chromosomal protein 1 (HMGB1) level in a rat model of sepsis created by cecal ligation and puncture (CLP).
  
  
  METHODS
  Rats received either CLP-induced sepsis or had additional immunoglobulin treatment in 1,500 or 300 mg/kg. After induction of sepsis and respective treatment conditions, pulmonary and renal tissues were examined histologically for pathological changes at postoperative hour (POH) 4, and serum cytokine and HMGB1 levels were measured at POH 4, 8, 20, and 44. Using other rats, we also observed the survival rate after CLP for 7 days.
  
  
  RESULTS
  Treatment with immunoglobulin significantly improved survival rate at postoperative day 7 (73% in the high-dose group vs. 33% in the control group; p = 0.037). The serum lactate dehydrogenase, endotoxin, creatinine, and blood urea nitrogen levels were significantly lower in the high-dose group than in the other groups. The serum HMGB1 level had increased at 4 h postoperatively in the control group (10.2 ± 3.3 ng/mL) and low-dose group (10.3 ± 4.0 ng/mL), but it was significantly reduced in the high-dose group (4.2 ± 0.8 ng/mL) compared with the control group (p = 0.03).
  
  
  CONCLUSIONS
  Our results suggest that high-dose immunoglobulin therapy may improve the serum endotoxin and HMGB1 levels and overall survival rate in sepsis by inhibiting the inflammation.
authors: Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors: Takahisa
authors: T
authors: Yoshikawa
authors: Hiroya
authors: H
authors: Takeuchi
authors: Koichi
authors: K
authors: Suda
authors: Taku
authors: T
authors: Miyasho
authors: Shingo
authors: S
authors: Yamada
authors: Minoru
authors: M
authors: Okamoto
authors: Yoshio
authors: Y
authors: Kawamura
authors: Ikuro
authors: I
authors: Maruyama
authors: Masaki
authors: M
authors: Kitajima
authors: Yuko
authors: Y
authors: Kitagawa
mesh_terms: D000818:Animals; D002432:Cecum / Q000601:surgery; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D006609:High Mobility Group Proteins / Q000097:blood*; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000008:administration & dosage*; D007668:Kidney / Q000473:pathology; D008026:Ligation; D008168:Lung / Q000473:pathology; D008297:Male; D011677:Punctures; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000401:mortality*; D012772:Shock, Septic / Q000401:mortality
chemical_list: D016207:Cytokines; D006609:High Mobility Group Proteins; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors