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Thromb Haemost 2004; 91(06): 1194-1201
DOI: 10.1160/TH03-09-0595
Wound Healing and Inflammation/Infection
Schattauer GmbH

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

Ken-ichiro Inoue
1   Inhalation Toxicology Research Team
2   Pathophysiology Research Team, National Institute for Environmental Studies,Tsukuba, Ibaraki
,
Hirohisa Takano
1   Inhalation Toxicology Research Team
3   Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto
,
Rie Yanagisawa
1   Inhalation Toxicology Research Team
2   Pathophysiology Research Team, National Institute for Environmental Studies,Tsukuba, Ibaraki
,
Miho Sakurai
1   Inhalation Toxicology Research Team
2   Pathophysiology Research Team, National Institute for Environmental Studies,Tsukuba, Ibaraki
,
Akinori Shimada
4   Department of Vaterinary Pathology, Faculty of Agriculture,Tottori University,Tottori
,
Takehito Morita
4   Department of Vaterinary Pathology, Faculty of Agriculture,Tottori University,Tottori
,
Masahiko Sato
5   Department of Hygienics, Gifu Pharmaceutical University, Gifu
,
Shin Yoshino
6   Department of Pharmacology, Kobe Pharmaceutical University, Kobe
,
Toshikazu Yoshikawa
3   Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto
,
Chiharu Tohyama
7   Environmental Health Science Division, National Institute for Environmental Studies,Tsukuba, Ibaraki, Japan
› Author Affiliations
Further Information

Publication History

Received 24 September 2003

Accepted after resubmission 12 February 2004

Publication Date:
02 December 2017 (online)

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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
 

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