COMPARISON OF THE CAPACITY OF RHTNF-ALPHA AND ESCHERICHIA-COLI TO INDUCE PROCOAGULANT ACTIVITY BY BABOON MONONUCLEAR-CELLS IN-VIVO AND IN-VITRO

The procoagulant activity of mononuclear cells (MNCs) may play an impo rtant role in the disseminated intravascular coagulation seen in septi c shock. This study compares the capacity of Escherichia coli (E. coli ) and recombinant human TNF-alpha (rhTNF-alpha) to induce procoagulant activity by baboon MNCs. in vivo studies showed that MNC procoagulant activity was significantly increased at T + 120 min after LD(100) E. coli infusion into baboons, Most of this procoagulant activity was att ributable to tissue factor. In contrast, a bolus infusion of rhTNF-alp ha (150 mu g/kg) and a monoclonal antibody to activated protein C (2 m g/kg) did not induce any increase of MNC procoagulant activity at T 120 min even though the plasma TNF-alpha level was 10 times higher tha n that seen following infusion of E. coli. In vitro studies showed tha t E. coli at concentrations comparable to that observed in the in vivo study and LPS at a concentration of 2.5 ng/mL induced more intense ti ssue factor expression by both human and baboon monocytes than rhTNF-a lpha in the concentrations ranging from 10 to 1,000 ng/mL. These resul ts suggest that TNF-alpha alone is not sufficient to induce noticeable MNC procoagulant activity, at least, in the early stage of this septi c shock model.