HUMAN INTERLEUKIN-6 ACTS AS A COFACTOR FOR THE UP-REGULATION OF C3 PRODUCTION BY RAT-LIVER EPITHELIAL-CELLS

We investigated the role of human interleukin-6 (IL-6) in the regulati on of the third component of complement (C3) biosynthesis by cultured rat liver epithelial cells. A natural human IL-6 (nh IL-6) preparation was shown to up-regulate C3 production, whereas an Escherichia coli-d erived recombinant human IL-6 (rh IL-6) displayed no activity on C3 bi osynthesis. However, the C3-stimulating activity of the nh IL-6 prepar ation was only partially reduced when treated with an antihuman IL-6 m onoclonal antibody. Binding studies indicated that although it was dev oid of any C3 stimulating activity, rh IL-6 specifically bound to hepa tic cell receptors (Kd = 0.38 nM) and possessed the same binding affin ity as nh IL-6. Furthermore, the substitution of natural IL-6 molecule s for the recombinant IL-6 led to the recovery of the initial C3-stimu lating activity. These studies demonstrate that human IL-6 alone does not stimulate rat liver epithelial cell C3 production but is able to a ccentuate the C3-stimulating activity of unrecognized components which are present in the nh IL-6 preparation. Human IL-6 thus appeal's to a ct asa co-factor for the up-regulation of hepatic C3 production.