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

Summary

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?, macrophage inflammatory protein (MIP)-1a., MIP-2, macrophage chemoattractant protein1, 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.

Keywords

Interleukin-6 - hemostatic and coagulatory change - lipopolysaccharide - cytokine

• References

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