Interferon exerts a cytotoxic effect on primary human myeloma cells.
A dye exclusion method was used for testing the sensitivity of primary human myeloma and normal bone-marrow cells to interferon (IFN). Following 4 days of incubation with 5000 units/ml of natural (n) IFN-alpha, there was a greater than 90% decrease in the number of viable myeloma cells in cultures from some patients, whereas myeloma cells from other patients showed intermediate or no sensitivity to IFN. The number of viable non-malignant bone-marrow cells (from the same patients) following a 4-day exposure to nIFN-alpha (5000 units/ml) decreased by 10-60%. Exposure of malignant and non-malignant bone-marrow cells to natural beta- and recombinant alpha- and gamma-IFN, also induced a decrease in the number of viable cells. The decreased number of viable myeloma cells could be observed already after 1 day of exposure to IFN-alpha in vitro. To test whether inhibition of proliferation could account for the observed effects, proliferation, as measured by [3H]thymidine uptake, was studied in some experiments. Only approx. 1-2% of the myeloma cells were labeled with [3H]thymidine during the 4 days of culture in vitro, whereas the proportion of labeled non-malignant cells was approx. 40%. Thus, the IFN-induced reduction of cell number in normal bone-marrow cells could possibly be attributed to a cell multiplication inhibitory effect of IFN, whereas the effect observed in myeloma cells cannot be attributed to cell multiplication inhibition. To test the possibility that the reduction in the number of myeloma cells could be attributed to the activity of autologous cytotoxic T-cells, NK-cells or macrophages, these cells were depleted in some experiments. Depletion of these cells did not, however, influence the IFN-induced decrease in the number of viable myeloma cells. We thus conclude that IFN can reduce the number of viable tumor cells by a cytotoxic effect, unrelated to cell multiplication inhibition.
D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D012737:Sex Factors; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects
D007370:Interferon Type I; D007371:Interferon-gamma