TNF-ALPHA SUPPRESSES IL-1-ALPHA AND IL-6 UP-REGULATION OF C4B-BINDINGPROTEIN IN HEPG-2 HEPATOMA-CELLS

C4b-binding protein (C4BP) is a regulatory protein involved in the reg ulation of the classical pathway of complement and the natural anticoa gulant pathway. C4BP is synthesized by the liver, a target organ of th e IL-6 proinflammatory cytokine. C4BP is an acute-phase protein and it s basal levels may increase by as much as 4-fold during an inflammator y response. IL-6 which plays a major role in the modulation of the acu te-phase proteins, including C4BP, also has been shown by our group to significantly increase hepatocyte production of the anticoagulant pro tein, protein S. In this study, we have examined the role of cytokine combinations on the production of the C4BP regulatory protein in the H epG-2 hepatoma cell line and report that IL-1 alpha and IL-6 in combin ation as well as IL-1 alpha and Oncostatin M (OSM) were approximately additive in the upregulation of C4BP while IL-6 and OSM were not and t hat TNF-alpha blocked bath IL-1 alpha and IL-6 but not OSM upregulatio n of C4BP.