炎症に伴う凝固・線溶異常におけるIL-6の保護的役割

Although the role of interleukin(IL)-6 in inflammatory disease has been previously examined, its role in hemostasis, fibrinolysis, and coagulation during inflammation remins to be established. The present study reviewed the role of IL-6 in hemostatic and coagulatory changes during inflammation, with special emphasis on the inflammation induced by intraperitoneal administration of lipopolysaccharide in IL-6 null-/- mice and corresponding wild type(WT) mice. After LPS challenge, IL-6-/- mice revealed significant prolongation of prothrombin time and partial thromboplastin time and a significant decrease in platelet counts as compared with WT mice. LPS treatment induced marked pulmonary hemorrahage 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 in the lungs were significantly greater in IL-6-/- mice than in WT mice after LPS challenge. Our results conclude that IL-6 is protective against coagulatory and hemostatic disturbance and subsequent pulmonary hemorrhage induced by bacterial endotoxin, at least party, via the modulation of proinflammatory processes. In addition, our studies suggest that anti-IL-6 therapy may not be efficient for systemic inflammatory disease such as disseminated intravascular coagulation, acute lung injury, and sepsis.