In vitro and in vivo effects of recombinant interferon gamma on the growth of hematopoietic progenitor cells from patients with myelodysplastic syndrome.

Recombinant interferon gamma (rIFN-gamma) has been shown to have antiproliferative effects on normal and leukemic hematopoietic cells, to induce cell differentiation and to modulate hematopoietic growth factor production. We have studied the effects of rIFN-gamma on the growth of hematopoietic progenitors from 3 patients with myelodysplastic syndrome who were treated with rIFN-gamma (0.01 mg/m2 given subcutaneously three times a week) as part of an Italian pilot study. When bone marrow cells were cultured in semisolid medium in the continuous presence of rIFN-gamma (10-10(4) U/ml), inhibition of colony formation was the most common response. However, an enhancement of hematopoietic progenitor growth was observed in one patient at the lowest concentration tested (10 U/ml). Preincubation of bone marrow mononuclear cells with low concentrations of rIFN-gamma in suspension culture for 5 days induced or enhanced in vitro colony formation in two cases; again, higher concentrations resulted in inhibition of hematopoietic progenitor growth. Two patients showed a slight improvement of in vitro progenitor growth after one month of treatment with rIFN-gamma. Although preliminary, these data indicate that rIFN-gamma may have both stimulatory and inhibitory effects on myelodysplastic hematopoiesis, depending on both the effective concentrations and the interactions with accessory cells.