Suppressive effect of human interferons on erythroid colony growth in disorders of erythropoiesis

The suppressive effect of two types of human interferon (fibroblast and leukocyte types) on bone marrow and peripheral blood erythroid colony formation by cells from patients with various disorders of erythropoiesis was studied. Bone marrow or peripheral blood mononuclear cells were isolated and cultured in plasma clots with Epo, and benzidine-positive erythroid colonies counted after 7 to 14 days' incubation. Specimens included cells from patients with thalassemia, sickle cell anemia, secondary polycythemia, nutritional anemia, hemolytic anemia, refractory anemia, and normal controls. Results show that with the exception of nutritional anemia cells, erythroid colony formation by all specimens was significantly inhibited (84% to 100%) by 100 to 200 U of either interferon type per milliliter. Erythroid colony formation by nutritional anemia bone marrow cells ws inhibited only 30% to 40% by 200 U/ml fibroblast or leukocyte interferon, and 100 U/ml were ineffective. Sickle cell peripheral blood mononuclear cells and refractory anemia bone marrow demonstrated marked inhibition of colony formation (86% to 97%) with 50 U/ml fibroblast or leukocyte interferon. Inhibition of colony formation by sickle cell peripheral blood mononuclear cells was completely abolished by addition of anti-interferon. Colony formation by refractory anemia bone marrow was inhibited 46% to 51% by as little as 10 U/ml fibroblast or leukocyte interferon. This concentration of interferon was ineffective with cells from thalassemia, secondary polycythemia, nutritional anemia, hemolytic anemia, and controls. Mouse bone marrow colony formation was not suppressed by 200 U/ml leukocyte interferon. These results demonstrate that fibroblast or leukocyte interferons inhibit in vitro erythroid colony formation by human bone marrow or peripheral blood mononuclear cells, the effect is abolished by anti-interferon, and inhibition may be species-specific. These studies reveal that cells obtained from certan patients are particularly sensitive to the cytoxic effects of interferon, and it may be useful to monitor the erythropoietic state of the patient during interferon chemotherapy.