Rapid Publication Regulation of the Fibrinolytic System of Cultured Human

We examined the effects of human interleukin 1 (IL-1) on the production of fibrinolytic components by cultured human vascular endothelium. Conditioned media collected from IL-i-treated (5 U/ml, 24 h) monolayers exhibited decreased tissue-type plas-minogen activator (tPA) activity and increased plasminogen ac-tivator inhibitor (PAI) activity, as assessed by fibrin and reverse fibrin-autography. Quantitative immunological assays revealed a 35 % decrease in tPA antigen and a 360 % increase in active PAI antigen, after incubation for 24 h with 0.6 U/ml IL-1. Max-imal effects (-50 % decrease in tPA antigen; 400-800 % increase in active PAI antigen) were observed with 2.5-5 U/ml IL-1. Changes in tPA and PAI reached a maximum at '-24 h and persisted for>48 h. IL-1 induction of endothelial procoagulant activity was more rapid and transient, peaking by 6 h and'sub-siding by 24 h. Natural monocyte-derived IL-1 and two species of recombinant IL-i had comparable effects. Heat and poly-myxin-B treatments differentiated IL-1 actions from those of endotoxin, which promoted similar endothelial alterations. IL-1 effects on endothelial procoagulant and fibrinolytic activities may contribute to the generation and maintenance of fibrin in pathophysiological settings in vivo