TNF-ALPHA SUPPRESSES IL-6 UP-REGULATION OF PROTEIN-S IN HEPG-2 HEPATOMA-CELLS

The pathogenesis of disseminated intravascular coagulation (DIC) has, in part, been attributed to the impairment of the natural anticoagulan t protein C/protein S pathway. DIG, which frequently occurs during sep sis, has been linked to cytokines that can induce or modulate procoagu lant activity. Three of these cytokines, IL-1 alpha, IL-6, and TNF-alp ha have been reported to be increased in the early stages of sepsis. I n the present study, we have stimulated HepG-2 hepatoma cell cultures with recombinant human IL-la, IL-6, TNF-alpha, and oncostatin M (OSM). The results demonstrated that TNF-alpha, and to a lesser degree, IL-1 alpha, could significantly suppress IL-6 upregulation of protein S, w hereas the effects of OSM was only suppressed by the combination of IL -1 alpha and TNF-alpha. The combination of IL-1 alpha and TNF-alpha al so suppressed protein S production below that of control or basal leve ls. These results indicate that IL-1 alpha and TNF-alpha may play impo rtant regulatory roles in coagulation.