Inhibition of tissue factor and cytokine release.
The effect of inhibitors of cytokine release and plasma coagulation on lipopolysaccharide (LPS)-induced tissue factor and interleukin-6 (IL-6) was investigated. Dexamethasone, an inhibitor of cytokine production, inhibited LPS-induced tissue factor and IL-6 release by mononuclear cells (MNC), but enhanced IL-1beta-evoked tissue factor activity. Clinical antithrombin (AT) concentrates inhibited, in a dose-dependent manner, tissue factor and IL-6 production by MNC and human umbilical vein endothelial cells (HUVEC). The three AT preparations tested, when compared using the same antithrombin unit, had different potencies. Activated protein C (APC) augmented LPS stimulation of HUVEC and further increased the production of tissue factor and IL-6. The same effect was not observed with MNC; LPS-induced tissue factor and IL-6 release were unaffected by APC. Truncated tissue factor pathway inhibitor (TFPI1-161) inhibited LPS-induced MNC tissue factor and IL-6 production, but was unable to prevent LPS stimulatory activity on HUVEC. These data suggest a complex interaction between the coagulation pathway and the cytokine network.
National Institute for Biological Standards and Control, Potters Bar, UK.
E
E
Gray
S
S
Thomas
Y
Y
Mistry
S
S
Poole
D001777:Blood Coagulation / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors*; D013925:Thromboplastin / Q000378:metabolism*
D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D013925:Thromboplastin