Expression of tissue factor and interleukin-1 beta in a novel rabbit model of disseminated intravascular coagulation induced by carrageenan and lipopolysaccharide

Pathobiology. 1995;63(6):328-40. doi: 10.1159/000163969.


Thrombus formation and the sequential expression of tissue factor (TF), interleukin-1 beta (IL-1 beta) and interleukin-1 receptor antagonist (IL-1 ra) in several organs were examined immunohistochemically and morphometrically in a novel model of disseminated intravascular coagulation (DIC) developed by modifying the generalized Shwartzman reaction (GSR) in rabbits. The new model [carrageenan (CA)-lipopolysaccharide (LPS)] was induced by the administration of a priming dose of intraperitoneal CA, 10 mg/kg, followed 24 h later by a provocative dose of LPS 25 micrograms/kg, while GSR was induced by the intravenous injection of two doses of LPS 25 micrograms/kg. CA was detected predominantly within macrophages in the spleen and liver. Fibrin thrombi were formed as early as 1 h after the second LPS treatment in all examined organs reaching a peak at 3-9 h and their prevalence was higher in the CA-LPS group (p < 0.05). The sequential expressions of TF and IL-1 beta correlated well with each other in both groups reaching a peak at 3-9 h with the CA-LPS group showing a more pronounced expression than the GSR group. Macrophages in the liver, spleen and lungs, and Bowman's epithelial cells expressed both proteins, while IL-1 beta was also expressed by endothelial and epithelial cells. IL-1 ra was expressed by the same cells expressing IL-1 beta, however, its expression continued to increase gradually over 24 h. The mortality rate was lower (p < 0.05) and neutrophilic sequestration less prominent in the CA-LPS group than in the GSR group. These findings indicate that CA efficiently replaced the priming LPS treatment and the consequently enhanced production of IL-1 beta may have resulted in the upregulation of TF expression leading to the high level of thrombi in this new model which may provide a tool for further studies on the role of cytokines in DIC.

MeSH terms

  • Animals
  • Carrageenan* / metabolism
  • Disease Models, Animal*
  • Disseminated Intravascular Coagulation / etiology*
  • Disseminated Intravascular Coagulation / immunology
  • Disseminated Intravascular Coagulation / pathology
  • Female
  • Immunohistochemistry
  • Injections, Intraperitoneal
  • Injections, Intravenous
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / metabolism*
  • Kidney / metabolism
  • Kidney / pathology
  • Lipopolysaccharides*
  • Liver / metabolism
  • Liver / pathology
  • Lung / metabolism
  • Lung / pathology
  • Rabbits
  • Shwartzman Phenomenon
  • Sialoglycoproteins / metabolism
  • Spleen / metabolism
  • Spleen / pathology
  • Thromboplastin / metabolism*
  • Thrombosis / etiology
  • Thrombosis / pathology
  • Time Factors
  • Tissue Distribution


  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Lipopolysaccharides
  • Sialoglycoproteins
  • Carrageenan
  • Thromboplastin