Recombinant gamma-interferon and lipopolysaccharide enhance 1,25-dihydroxyvitamin D3-induced cell differentiation in human promyelocytic leukemia (HL-60) cells.

The induction of cell differentiation by a combination of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], recombinant gamma-interferon (rec gamma-IFN), and a lipopolysaccharide from E. coli (LPS) was studied in a clonal population (clone-9) of human promyelocytic HL-60 leukemia cells in vitro. Treatment of clone-9 cells with 10(-9) to 10(-7)M 1,25-(OH)2D3 yielded a macrophage cell differentiation. The addition of 10 or 100 U/ml of gamma-IFN and 2 or 10 micrograms/ml LPS caused a further increase in expression of the different differentiation markers. The most pronounced effects involved increases in cell attachment to the surface of tissue-culture Petri dishes and in lysozyme, nonspecific esterase, and cytolytic activities. The combined treatment with 1,25-(OH)2D3 and rec gamma-IFN and LPS also caused an increase in the percent of multinucleated giant cells. These results indicate the effectiveness of combining different agents in inducing cell differentiation in HL-60 cells. A similar approach may be useful in controlling myeloid leukemias in vivo.