Echinomycin suppresses the pyrogenic effects of endotoxin and interleukin-1 beta in human endothelial cells and peripheral blood mononuclear cells.

Endotoxin (LPS) and interleukin-1 beta (IL-1 beta) increased in a dose-dependent manner the expression of tissue factor, an ubiquitous membrane-anchored glycoprotein that initiates blood coagulation at the surface of human umbilical vein endothelial cells (HUVEC and human peripheral blood mononuclear cells (PBMC). Echinomycin, a cyclic octapeptide of microbial origin strongly inhibited LPS- and IL-1 beta-induced tissue factor expression in HUVEC and PBMC with IC50 values in the subnanomolar range at the same time it reduced LPS and IL-1 beta-induced expression of intercellular adhesion molecule-1 (ICAM-1, CD54) on HUVEC (IC50 = 0.4 +/- 0.1 and 0.3 +/- 0.2 nM respectively). Echinomycin also reduced LPS-induced secretion of IL-1 beta and IL-6 by human PBMC (IC50 = 10 +/- 2 and 3 +/- 0.5 nM respectively). These observations demonstrate that echinomycin protects endothelial cells and PBMC from the pyrogenic effect of LPS and IL-1 beta.