FIBRINOLYTIC RESPONSE TO INTERFERON-ALPHA IN HEALTHY-HUMAN SUBJECTS

Interferons (IFNs) are used for a variety of disorders. It has been po stulated that part of the effects of IFN may be mediated by IFN-induce d modulation of endothelial cells. Since the principal activating and inhibiting factors of the fibrinolytic system are synthesized and stor ed in endothelial cells. we have studied the effects on fibrinolysis a nd coagulation of the administration of recombinant IFN-alpha (5 X 10( 6) U/m(2)) to healthy human subjects (n = 8) in a randomized controlle d cross-over study. IFN-alpha significantly increased plasma levels of tissue-type plasminogen activator (t-PA) and urokinase-type plasminog en activator (u-PA). Simultaneously, plasma levels of the inhibitor of plasminogen activation, PAI-1, sharply increased. The net effect on p lasma plasminogen activator activity (PA-activity) was a modest increa se to 116% of baseline, however without a significant effect on plasmi n generation, as reflected by plasma levels of plasmin-alpha(2)-antipl asmin complexes. IFN-alpha had no effect on the plasma levels of throm bin-antithrombin III (TAT) complexes. We conclude that despite conside rable effects on endothelial cells, IFN-alpha does nor significantly a lter the coagulant-fibrinolytic balance, although the occurrence of su ch changes under pathological circumstances is not excluded.