Differentiation‐inducing and cytotoxic effects of tumor necrosis factor and interferon‐gamma in myeloblastic ML‐1 cells

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Abstract
The effects of the tumor necrosis factor (TNF), and a second pleiotropic cytokine interferon-gamma (IFN), were examined in a line of human myeloblastic leukemia cells (ML-1). By itself, TNF causes ML-1 to differentiate along the monocytic pathway. The cells exhibit an increase in Fc receptors and acquire the morphological characteristics of maturing phenotype. They remain viable and continue to proliferate (at ≥ 50% of the control growth rate) even with 102–104 units/ml TNF. IFN alone has similar effects, causing an increase in Fc receptors but little cytotoxicity. In contrast to either cytokine alone, the combination of TNF plus IFN causes a cessation of proliferation and extensive cell death. Cytotoxicity occurs in a synergistic fashion; it requires the simultaneous presence of both cytokines, occurring with concurrent but not sequential exposure. These different responses, differentiation (TNF alone) and cytotoxicity (TNF + IFN), occur with a similar range of doses (∼ 102–104 units/ml) and in a similar time frame (beginning on day 2). In other cell types, IFN can augment either the differentiation-inducing or the cytotoxic effect of TNF. In ML-1, the combined application of TNF plus IFN results in a shift from differentiation to cytotoxicity.