MODULATION OF THE ENDOTHELIAL PROCOAGULANT RESPONSE TO LIPOPOLYSACCHARIDE AND AND TUMOR-NECROSIS-FACTOR-ALPHA IN-VITRO - THE EFFECTS OF DEXAMETHASONE, PENTOXIFYLLINE, ILOPROST AND A POLYCLONAL ANTI-HUMAN IL-1-ALPHA ANTIBODY

Endothelial expression of tissue factor (TF), a potent procoagulant mo lecule, is increased in response to inflammatory mediators such as lip opolysaccharide (LPS), tumour necrosis factor (TNF) and interleukin-1 (IL-1). We have examined the effects of three antiinflammatory agents and a polyclonal anti-human IL-1 alpha antibody on the human endotheli al TF response to E. coli 0111:B4 LPS and recombinant TNF alpha (rTNF alpha) in vitro. In contrast to the expected inhibitory effect, dexame thasone, pentoxyfilline and iloprost failed to block TF expression whe n administered simultaneously or 30 minutes prior to stimulation with either LPS or rTNF alpha. Inhibition of procoagulant activity was demo nstrated with the anti-IL-1 alpha antibody, suggesting that endothelia l derived IL-1 alpha is partially responsible for the TF response to t he agonists employed. The failure of the antiinflammatory agents to in hibit endothelial TF expression highlights the possibility that therap eutic agents that modulate the circulating monocyte response to LPS an d TNF alpha may not ameliorate the endothelial dysfunction that is als o induced by these inflammatory mediators.