INTERLEUKIN-6 UP-REGULATES TNF-ALPHA-DEPENDENT C3-STIMULATING ACTIVITY THROUGH ENHANCEMENT OF TNF-ALPHA SPECIFIC BINDING ON RAT-LIVER EPITHELIAL-CELLS

The authors investigated the role of tumour necrosis factor alpha (TNF -alpha) and interleukin 6 (IL-6), two major pro-inflammatory cytokines , in the stimulation of the third component of complement (C3) product ion by rat Liver epithelial cells, Though often considered as the-most potent inflammatory cytokine, IL-6 alone displayed no activity, where as TNF-alpha upregulated C3 production in a dose-dependent manner, How ever, IL-6 was shown to synergistically stimulate C3 production in the presence of TNF-alpha, To account for this interaction, it was postul ated that IL-6 modulates the binding of TNF-alpha on liver target cell s, That IL-6 increased the binding of TNF-alpha on the surface of the hepatic cells, whereas TNF-alpha alone downregulated its own specific binding capacity is reported, Furthermore, this upregulatory effect of IL-6 was mainly attributable to an increase in the number of plasma m embrane TNF-alpha specific receptors, with little change in their affi nity, These results suggest that the synergistic IL-6 activity on C3 p roduction may occur, at least partially, through its capacity to upreg ulate the number of TNF-alpha receptors on the surface of the rat live r epithelial cells. (C) 1996 Academic Press Limited.