IL-4 and IL-13 exhibit comparable abilities to reduce pyrogen-induced expression of procoagulant activity in endothelial cells and monocytes.
Endotoxin (LPS), interleukin-1 beta (IL-1) and tumor necrosis factor-alpha (TNF) increased the expression of tissue factor, a membrane-anchored glycoprotein that initiates blood coagulation on the surface of cultured bovine aortic endothelial cells (ABAE) and human monocytes. These compounds simultaneously reduced the amount of thrombomodulin on the endothelial cell surface, further contributing to the procoagulant activity of the endothelium or monocytes. On endothelial cells and monocytes, interleukin-4 (IL-4) and interleukin-13 (IL-13), a newly described lymphokine, both strongly inhibited LPS-induced tissue factor expression, a similar activity also being obtained with regard to the pyrogenic effects of IL-1 or TNF. When measured in parallel, IL-4 and IL-13 counteracted thrombomodulin down-regulation induced by LPS, IL-1 or TNF in endothelial cells. These results therefore show that both IL-4 and IL-13 protect the endothelial and the monocyte surface against inflammatory mediator-induced procoagulant changes.
Herbert
J M
JM
Sanofi Recherche, Hemobiology Research Department, Toulouse, France.
Savi
P
P
Laplace
M C
MC
Lalé
A
A
Dol
F
F
Dumas
A
A
Labit
C
C
Minty
A
A
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D002417:Cattle; D002478:Cells, Cultured; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D007375:Interleukin-1 / Q000494:pharmacology; D018793:Interleukin-13; D015847:Interleukin-4 / Q000494:pharmacology*; D007378:Interleukins / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D011749:Pyrogens / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D018179:Receptors, Thrombin; D013917:Thrombin / Q000378:metabolism; D013925:Thromboplastin / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D018793:Interleukin-13; D007378:Interleukins; D008070:Lipopolysaccharides; D011749:Pyrogens; D011956:Receptors, Cell Surface; D018179:Receptors, Thrombin; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D013925:Thromboplastin; D013917:Thrombin