SELECTIVE REGULATION BY HYDROCORTISONE OF INDUCTION OF INVIVO DIFFERENTIATION OF MYELOID LEUKEMIC-CELLS WITH GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR, INTERLEUKIN-6 AND INTERLEUKIN-1-ALPHA

Clones of myeloid leukemic cells can differ in their ability to be induced to differentiate in vitro by different cytokines. Using such leukemic clones, we studied the regulation by hydrocortisone of induction of in vivo differentiation by injection of recombinant interleukin 6 (IL-6), interleukin 1(alpha) (IL-1(alpha)), and granulocyte-macrophage colony-stimulating factor (GM-CSF). Injection of IL-6 and IL-1(alpha) induced in vivo differentiation of leukemic cells that were induced to differentiate by these cytokines in vitro, but not of leukemic cells that were not susceptible to these cytokines in vitro. In contrast, injection of GM-CSF induced in vivo differentiation both in leukemic cells that were susceptible or not susceptible to GM-CSF in vitro. The effect of GM-CSF, but not of IL-6 or IL-1(alpha), on inducing differentiation in vivo was inhibited by pretreatment with hydrocortisone. In leukemic cells that were not induced to differentiate with GM-CSF in vitro, this inhibition of differentiation by pretreatment with hydrocortisone was greater than inhibition of differentiation obtained by pretreatment with cyclophosphamide or irradiation or the use of nude mice. After hydrocortisone pretreatment, the number of peritoneal cells and their ability to produce GM-CSF and IL-6 were suppressed. It is suggested that hydrocortisone can inhibit the effect of an injected cytokine such as GM-CSF on induction of in vivo differentiation of leukemic cells by inhibiting the ability of host cells to produce cytokines to which the leukemic cells are susceptible.