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-alpha) and human transforming growth factor-beta (hTGF-beta) potently inhibited B9 and to a lesser extent 7TD1 cells, while hIL-11, human oncostatin M (hOSM), and human leukemia inhibitory factor (hLIF) had no inhibitory 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 required to induce maximal cell proliferation. Increasing concentrations of IL-6 (up to 100 ng/ml) could not overcome the antiproliferative effects of mIFNs, hTNF-alpha and hTGF-beta. Supernatants from mIFN-gamma and 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 detectable IL-6 bioactivity. However, diluted samples contained considerable amounts of detectable IL-6 bioactivity (nanogram levels). Testing the same samples for IL-6 immunoreactivity using enzyme-linked immunoabsorbent 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.
Schwabe
M
M
Laboratory of Biochemical Physiology, Biological Response Modifiers Program, National Cancer Institute, Frederick, MD 21702, USA.
Cox
G W
GW
Bosco
M C
MC
Prohaska
R
R
Kung
H F
HF
D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006825:Hybridomas / Q000166:cytology / Q000187:drug effects*; D007372:Interferons / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D010954:Plasmacytoma / Q000276:immunology* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000093242:Interleukin-6 Inhibitors
D016207:Cytokines; D006131:Growth Inhibitors; D007372:Interferons; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors