MULTIPLE CYTOKINES INHIBIT INTERLEUKIN-6-DEPENDENT MURINE HYBRIDOMA PLASMACYTOMA PROLIFERATION/

A panel of cytokines was tested for inhibitors of interleukin-6 (IL-6) -dependent cell proliferation. Murine type I and II interferons (mIFNs ) strongly inhibited proliferation of IL-6-dependent B9 and 7TD1 cells in a dose-dependent manner. Human tumor necrosis factor-alpha (hTNF-a lpha) and human transforming growth factor-beta (hTGF-beta) potently i nhibited B9 and to a lesser extent 7TD1 cells, while hIL-11, human onc ostatin M (hOSM), and human leukemia inhibitory factor (hLIF) had no i nhibitory effects on IL-6-dependent growth, Conversely, IL-11 and OSM but not LIF stimulated B9 and 7TD1 cell growth, However, compared with IL-6, up to 1000-fold higher IL-11 and OSM concentrations were requir ed to induce maximal cell proliferation. Increasing concentrations of IL-6 (up to 100 ng/ml) could not overcome the antiproliferative effect s of mIFNs, hTNF-alpha, and hTGF-beta. Supernatants from mIFN-gamma an d lipopolysaccharide (LPS)-treated mouse macrophages (ANA-1 cell line) were tested in B9 cell assays to identify cytokines among stimulatory and inhibitory biological activities that can inhibit IL-6-dependent proliferation, Undiluted or relatively concentrated supernatants from ANA-1 macrophages treated with mIFN-gamma and/or LPS did not contain d etectable IL-6 bioactivity. However, diluted samples contained conside rable amounts of detectable IL-6 bioactivity (nanogram levels), Testin g the same samples for IL-6 immunoreactivity using enzyme-linked immun oabsorbent assay revealed comparable levels of mIL-6, We conclude that IFNs, TNF-alpha, and TGF-beta and possibly other factors are potent, dominant inhibitors of IL-6-dependent plasmacytoma/hybridoma growth in vitro. (C) 1996 Academic Press, Inc.