Induction of Differentiation of Human Myeloid Cell Lines by Tumor Necrosis Factor in Cooperation with 1α,25-Dihydroxyvitamin D₃¹

We analyzed the combined effect of tumor necrosis factor and 1α,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 γ-interferon synergizes with each compound to induce differentiation. However, recombinant tumor necrosis factor is much more effective than recombinant γ-interferon in potentiating the effect of 1α,25-dihydroxyvitamin D₃ and, alone, is also more effective than recombinant γ-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 1α,25-dihydroxyvitamin D₃ on monocytic differentiation is discussed.