Tumor necrosis factor and interleukin 1 can act as essential growth factors in a murine plasmacytoma line

The survival and proliferation of the murine plasmacytoma cell line T1165 was previously shown to depend on a plasmacytoma growth factor (PCT-GF) produced by the murine P388D1 macrophage cell line. In the present study we examined several cytokines for their ability to stimulate the proliferation of T1165 cells. Recombinant human interleukin 6 (IL-6; also termed BSF-2 or interferon-beta 2) exhibited a potent growth stimulating effect on T1165 cells, with a maximal stimulation observed at 2 ng/ml or higher concentrations. Recombinant tumor necrosis factor (TNF) and recombinant interleukin 1 (IL-1) were found to produce a similar growth stimulation. Both murine and human TNF induced a maximal or near-maximal DNA synthesis in T1165 cells at 10 to 100 ng/ml after a 24-hr incubation. Phorbol myristate acetate (PMA) caused a weak stimulation of DNA synthesis in T1165 cells, and combined treatment with TNF and PMA resulted in an additive stimulation. The promotion of T1165 cell proliferation by TNF appeared to be the result of a direct action, as no autocrine growth factor could be detected in T1165 cultures after incubation with TNF. These results indicate that TNF and IL-1 can substitute for IL-6 as essential growth factors in a growth factor-dependent murine plasmacytoma line.