Protective role of interleukin-6 in coagulatory and hemostatic disturbance induced by lipopolysaccharide in mice.

Abstract

Although the role of interleukin (IL)-6 in inflammatory diseases has been previously examined, its role in hemostasis, fibrinolysis, and coagulation during inflammation remains to be established. The present study elucidated the role of IL-6 in hemostatic and coagulatory changes during severe inflammation induced by intraperitoneal administration of lipopolysaccharide (LPS: 1 mg/kg) using IL-6 null (-/-) mice. After LPS challenge, IL-6 (-/-) mice revealed significant prolongation of prothrombin time and activated partial thromboplastin time and a significant decrease in platelet counts as compared with wild type mice. LPS treatment induced marked pulmonary hemorrhage with neutrophilic inflammation in IL-6 (-/-) mice, in contrast, only mild neutrophilic infiltration in WT mice confirmed by macroscopic and histological findings. The protein levels of proinflammatory mediators, such as IL-1 beta, macrophage inflammatory protein (MIP)-1 alpha, MIP-2, macrophage chemoattractant protein-1, granulocyte/macrophage-colony-stimulating factor, and keratinocyte chemoattractant in the lungs were significantly greater in IL-6 (-/-) mice than in WT mice after LPS challenge. These results directly indicate that IL-6 is protective against coagulatory and hemostatic disturbance and subsequent pulmonary hemorrhage induced by bacterial endotoxin, at least partly, via the modulation of proinflammatory processes.

• Authors: Ken-ichiro Inoue, Hirohisa Takano, Rie Yanagisawa, Miho Sakurai, Akinori Shimada, Takehito Morita, Masahiko Sato, Shin Yoshino, Toshikazu Yoshikawa, Chiharu Tohyama
• Journal: Thrombosis and haemostasis (Thromb Haemost) Vol. 91 Issue 6 Pg. 1194-201 (Jun 2004) ISSN: 0340-6245 [Print] Germany
• PMID: 15175807 (Publication Type: Journal Article)

Chemical References

• Cytokines
• Interleukin-6
• Lipopolysaccharides

Topics

• Animals
• Blood Coagulation (drug effects)
• Cytokines (blood)
• Fibrinolysis (drug effects)
• Genotype
• Hemorrhagic Septicemia (blood, genetics)
• Hemostasis (drug effects)
• Inflammation
• Interleukin-6 (deficiency, genetics, physiology)
• Lipopolysaccharides (administration & dosage)
• Lung Diseases (blood, genetics, immunology)
• Mice
• Mice, Knockout