Role of interleukin-6 in fibrinolytic changes induced by lipopolysaccharide in mice.
We have recently demonstrated that interleukin (IL)-6 is protective against coagulatory and hemostatic disturbance and subsequent pulmonary hemorrhage induced by bacterial endotoxin, at least partly, via the inhibition of proinflammatory cytokines and chemokines using IL-6-null [IL-6(-/-)] mice and corresponding wild-type mice. Its role in fibrinolytic systems remains undefined, however. The present study elucidated the role of IL-6 in the activity of alpha(2)-plasmin inhibitor, an inhibitor of fibrinolysis, during inflammation induced by intraperitoneal administration of lipopolysaccharide in IL-6(-/-) and wild-type mice. Both IL-6(-/-) and wild-type mice were injected with vehicle or lipopolysaccharide (1 mg/kg). Seventy-two hours later, blood samples were collected and alpha(2)-plasmin inhibitor activity was examined. Lipopolysaccharide challenge induced significant enhancement of alpha(2)-plasmin inhibitor activity as compared with vehicle challenge in wild-type mice, but not in IL-6(-/-) mice. In the presence of lipopolysaccharide, the activity was significantly lower in IL-6(-/-) mice than that in wild-type mice. These results indicate that IL-6 can, at least partly, inhibit the lipopolysaccharide-enhanced fibrinolysis via the enhanced alpha2-plasmin inhibitor activity.
Inoue
Ken-ichiro
K
Inhalation Toxicology & Pathophysiology Research Team, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan.
Takano
Hirohisa
H
Yanagisawa
Rie
R
Sakurai
Miho
M
Shimada
Akinori
A
Sato
Masahiko
M
Yoshino
Shin
S
Yoshikawa
Toshikazu
T
D000818:Animals; D004195:Disease Models, Animal; D005342:Fibrinolysis / Q000187:drug effects* / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D007274:Injections, Intraperitoneal; D015850:Interleukin-6 / Q000172:deficiency / Q000276:immunology* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000979:alpha-2-Antiplasmin / Q000187:drug effects / Q000276:immunology
D015850:Interleukin-6; D008070:Lipopolysaccharides; D000979:alpha-2-Antiplasmin