Stimulation of differentiation of mouse myeloid leukemic cells and induction of interferon in the cells by double-stranded polyribonucleotides.

Mouse myeloid leukemic MI cells can be induced to differentiate into mature macrophages and granulocytes by differentiation-stimulating factor (D-factor) in conditioned medium of mouse peritoneal macrophages. Double-stranded RNA's, such as the copolymers of polyinosinic and polycytidylic acids and polyadenylic and polyuridylic acids, could not alone induce differentiation of the cells, but enhanced induction of differentiation by low concentrations of the D-factor and induced a significant amount of interferon. Rabbit antiserum to purified L-cell interferon neutralized the antiviral activity of interferon of MI cells. Simultaneous treatment of MI cells with the anti-interferon serum and copolymer of polyinosine and polycytidylic acids and D-factor abolished the enhancing effect of copolymer of polyinosine and polycytidylic acids on the action of the D-factor. These results suggest that the effect of double-stranded RNA's on induction of differentiation of MI cells is mediated by interferon produced by the cells.