Effects of hyperthermia and granulocyte-macrophage colony-stimulating factor on the differentiation of human leukemic cell line U937.

We have studied the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and hyperthermia individually and in combination on the cell growth and differentiation of human monoblastic leukemia cell line U937. Several criteria were used to evaluate the differentiation of these cells, including the reduction in the plating efficiency and cell growth, the ability to phagocytize latex particles, the reduction of nitro blue tetrazolium (NBT), and development of surface antigenic markers. Hyperthermia alone was able to inhibit cell proliferation, reduce cell viability, and induce differentiation. In the range of 41-43 degrees C, the major effect of hyperthermia was cell differentiation induction as judged by above criteria. On average, hyperthermia induced differentiation in 32% of cells. GM-CSF was able to induce differentiation in 37% of U937 cells as judged by similar criteria. The combined treatment with GM-CSF and hyperthermia resulted in the differentiation of 60% of U937 cells. The extent of differentiation obtained is comparable or better than other combinatorial treatments using various cytokines or cytokines and chemical reagents reported before.