title: No interplay between the pathways mediating coagulation and inflammation in tissue factor-induced disseminated intravascular coagulation in rats.
abstract: OBJECTIVE
  Previous reports have suggested an interplay between the pathways mediating coagulation and inflammation in endotoxemia and sepsis. The present study was designed to examine whether cross-signaling between the pathways mediating coagulation and inflammation occurs, as suggested by the pattern of cytokine production observed following tissue-factor (TF)-induced disseminated intravascular coagulation (DIC).
  
  
  METHODS
  Prospective, comparative, experimental study.
  
  
  METHODS
  Laboratory at a university hospital.
  
  
  METHODS
  Male Wistar rats, aged 6-7 wks, and weighing 160-170 g.
  
  
  METHODS
  Male Wistar rats were administered TF (3.75 units/kg every 4 hrs), TF, and tranexamic acid (TA; 50 mg/kg every 4.5 hrs) or lipopolysaccharide (30 mg/kg every 4 hrs) via the tail vein, and blood was sampled at 0, 4, 8 and 12 hrs.
  
  
  RESULTS
  Subsequent alterations in thrombin-antithrombin complex and fibrinogen levels, as well as platelet counts, indicated that the severity of both types of experimental DIC (TF-induced and lipopolysaccharide-induced) was similar with respect to hemostatic activation and development of consumption coagulopathy. In lipopolysaccharide-induced DIC, a sharp increase in plasma tumor necrosis factor levels was observed at 4 hrs, after which a sharp decline was noted. Plasma levels of interleukin-6 were markedly increased at 4 hrs, after which a sustained elevation was observed for the duration of the experimental period (tumor necrosis factor, 1270 +/- 280, 180 +/- 40, and 120 +/- 30 pg/mL at 4, 8 and 12 hrs, respectively; interleukin-6, 5810 +/- 1320, 4850 +/- 730, and 5230 +/- 1280 pg/mL at 4, 8 and 12 hrs, respectively). On the other hand, tumor necrosis factor and interleukin-6 were not detected following TF-induced DIC (0 +/- 0 at 4, 8, and 12 hrs for both tumor necrosis factor and interleukin-6). In the TF+TA group, significant increases in tumor necrosis factor and interleukin-6 were observed, compared with the TF group.
  
  
  CONCLUSIONS
  There is no overt interplay between the pathways mediating coagulation and inflammation in TF-induced DIC, as observed in lipopolysaccharide-induced DIC.
authors.affiliation: Department of Internal Medicine (III), Kanazawa University School of Medicine, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ontachi
authors.forename: Hidesaku
authors.initials: H
authors.lastname: Asakura
authors.forename: Yoko
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Tomoe
authors.initials: T
authors.lastname: Hayashi
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: Mika
authors.initials: M
authors.lastname: Omote
authors.forename: Tomotaka
authors.initials: T
authors.lastname: Yoshida
authors.forename: Masahide
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Eriko
authors.initials: E
authors.lastname: Morishita
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Shinji
authors.initials: S
authors.lastname: Nakao
mesh_terms: D000818:Animals; D000933:Antifibrinolytic Agents / Q000494:pharmacology; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism*; D004211:Disseminated Intravascular Coagulation / Q000139:chemically induced / Q000503:physiopathology*; D006490:Hemostatics / Q000494:pharmacology*; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D011446:Prospective Studies; D051381:Rats; D017208:Rats, Wistar; D020239:Receptor Cross-Talk / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013925:Thromboplastin / Q000494:pharmacology*; D014148:Tranexamic Acid / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000933:Antifibrinolytic Agents; D016207:Cytokines; D006490:Hemostatics; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D014148:Tranexamic Acid; D013925:Thromboplastin