title: Immunoglobulin preparations attenuate organ dysfunction and hemostatic abnormality by suppressing the production of cytokines in lipopolysaccharide-induced disseminated intravascular coagulation in rats.
abstract: OBJECTIVE
  We attempted to clarify the effect of immunoglobulin concentrates on the rat lipopolysaccharide (LPS)-induced disseminated intravascular coagulation (DIC) model.
  
  
  METHODS
  Prospective, comparative, experimental study.
  
  
  METHODS
  Laboratory at a university hospital.
  
  
  METHODS
  Male Wistar rats, aged 6 to 7 wks and weighing 160 to 170 g.
  
  
  METHODS
  Two kinds of experiments were performed. In the first, experimental DIC was induced by sustained infusion of 30 mg/kg LPS for 4 hrs via the tail vein, and two doses of immunoglobulin (25 or 100 mg/kg/4.5 hrs) were administered to rats 30 mins before infusion of LPS, after which immunoglobulin infusion was continued for a further 4 hrs. In the second, experimental DIC was induced by sustained infusion (5 mg/kg/1 hr) of LPS for 1 hr, and one dose of immunoglobulin (100 mg/kg/4 hrs) was administered to rats after LPS induction. The parameters were estimated at 4 hrs and 8 hrs in the first experiment and at 1, 5, and 10 hrs in the second one.
  
  
  RESULTS
  Similar results were observed in the two experiments. Consumption coagulopathy and hemostatic activation were attenuated, especially when immunoglobulin was administered before LPS infusion. Plasma levels of creatinine and alanine aminotransferase were significantly depressed by coadministration of immunoglobulin. Marked glomerular fibrin deposition was observed in the LPS-induced DIC model, but this deposition was reduced by immunoglobulin. In the first stage of the experiment, plasma levels of tumor necrosis factor (TNF) and interleukin (IL)-6 were suppressed by coadministration of immunoglobulin. In the second, plasma levels of IL-6 were significantly suppressed by immunoglobulin.
  
  
  CONCLUSIONS
  It was concluded that plasma levels of TNF and IL-6 could be significantly suppressed by immunoglobulin in the LPS-induced DIC model. Moreover, hemostatic abnormality, organ dysfunction, and glomerular fibrin deposition in this model were all ameliorated by immunoglobulin.
authors.affiliation: Department of Internal Medicine III, Kanazawa University School of Medicine, Ishikawa, Japan. HASAKURA@MED3.M.KANAZAWA-U.AC.JP
authors.forename: Hidesaku
authors.initials: H
authors.lastname: Asakura
authors.forename: Yoko
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Anna
authors.initials: A
authors.lastname: Kubo
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ontachi
authors.forename: Tomoe
authors.initials: T
authors.lastname: Hayashi
authors.forename: Mika
authors.initials: M
authors.lastname: Omote
authors.forename: Masahisa
authors.initials: M
authors.lastname: Arahata
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Kadohira
authors.forename: Mio
authors.initials: M
authors.lastname: Maekawa
authors.forename: Masahide
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Eriko
authors.initials: E
authors.lastname: Morishita
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Takami
authors.forename: Tomotaka
authors.initials: T
authors.lastname: Yoshida
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Shinji
authors.initials: S
authors.lastname: Nakao
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D004211:Disseminated Intravascular Coagulation / Q000188:drug therapy* / Q000209:etiology; D005337:Fibrin / Q000378:metabolism; D006487:Hemostasis / Q000187:drug effects; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage*; D007155:Immunologic Factors / Q000008:administration & dosage*; D015850:Interleukin-6 / Q000097:blood*; D007678:Kidney Glomerulus / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects; D008297:Male; D011446:Prospective Studies; D051381:Rats; D017208:Rats, Wistar; D048069:Tumor Necrosis Factors / Q000097:blood*
chemical_list: D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D015850:Interleukin-6; D008070:Lipopolysaccharides; D048069:Tumor Necrosis Factors; D005337:Fibrin; D003404:Creatinine; D000410:Alanine Transaminase