IL-4 AND IL-13 EXHIBIT COMPARABLE ABILITIES TO REDUCE PYROGEN-INDUCEDEXPRESSION OF PROCOAGULANT ACTIVITY IN ENDOTHELIAL-CELLS AND MONOCYTES

Endotoxin (LPS), interleukin-1beta (IL-1) and tumor necrosis factor-al pha (TNF) increased the expression of tissue factor, a membrane-anchor ed glycoprotein that initiates blood coagulation on the surface of cul tured bovine aortic endothelial cells (ABAE) and human monocytes. Thes e compounds simultaneously reduced the amount of thrombomodulin on the endothelial cell surface, further contributing to the procoagulant ac tivity of the endothelium or monocytes. On endothelial cells and monoc ytes, interleukin-4 (IL-4) and interleukin-13 (IL-13), a newly describ ed lymphokine, both strongly inhibited LPS-induced tissue factor expre ssion, a similar activity also being obtained with regard to the pyrog enic 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 T NF in endothelial cells. These results therefore show that both IL4 an d IL-13 protect the endothelial and the monocyte surface against infla mmatory mediator- induced procoagulant changes.