Protective role of interleukin-6 in coagulatory and hemostatic disturbance induced by lipopolysaccharide in mice.
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.
Inoue
Ken-ichiro
K
Inhalation Toxicology Research Team, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan.
Takano
Hirohisa
H
Yanagisawa
Rie
R
Sakurai
Miho
M
Shimada
Akinori
A
Morita
Takehito
T
Sato
Masahiko
M
Yoshino
Shin
S
Yoshikawa
Toshikazu
T
Tohyama
Chiharu
C
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D016207:Cytokines / Q000097:blood; D005342:Fibrinolysis / Q000187:drug effects; D005838:Genotype; D006483:Hemorrhagic Septicemia / Q000097:blood / Q000235:genetics; D006487:Hemostasis / Q000187:drug effects; D007249:Inflammation; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008171:Lung Diseases / Q000097:blood / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout
D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides