Induction of differentiation of human myeloid cell lines by tumor necrosis factor in cooperation with 1 alpha,25-dihydroxyvitamin D3.

We analyzed the combined effect of tumor necrosis factor and 1 alpha,25-dihydroxyvitamin D3 on the differentiation of human myeloid cell lines HL-60, ML3, and U937. The two compounds synergize in inducing the morphological, phenotypic, enzymatic, and functional characteristics of cells of the monocytic lineage. Immune gamma-interferon synergizes with each compound to induce differentiation. However, recombinant tumor necrosis factor is much more effective than recombinant gamma-interferon in potentiating the effect of 1 alpha,25-dihydroxyvitamin D3 and, alone, is also more effective than recombinant gamma-interferon in inducing expression of the high-affinity Fc receptor on ML3 cells. The possible physiological or pathological relevance of the synergistic effect of tumor necrosis factor and 1 alpha,25-dihydroxyvitamin D3 on monocytic differentiation is discussed.