Synergy among erythropoietin, interleukin 3, stem cell factor (c-kit ligand) and interferon-gamma on early human hematopoiesis.

The stimulatory effect of interferon-gamma (IFN-gamma) on human early hematopoiesis was investigated using CD34+ cells that were purified from peripheral blood as a target. In the presence of human interleukin 3 (IL-3) and stem cell factor (SCF), the growth of colony forming units for granulocyte/macrophage (CFU-GM) in serum-free methylcellulose culture was enhanced up to 5.5-fold over baseline colony formation (n = 10, mean +/- SE, 3.18 +/- 1.00) by coculture with 2.5 x 10(3) U/ml IFN-gamma, whereas burst forming units-erythroid (BFU-E) growth induced by additional erythropoietin (Epo) was reduced dose-dependently. Liquid-suspension culture of the target cells for 24 h with IFN-gamma before secondary plating in serum-free methylcellulose resulted in a marked increase in the colony numbers; 3.62 +/- 1.04-fold for CFU-GM and 5.72 +/- 2.32-fold for BFU-E (n = 5). The effect was most striking in the growth of erythroid lineage supported by Epo alone in serum-free culture. Delayed addition of IFN-gamma between days 4 and 7 of methylcellulose culture suppressed CFU-GM growth, but not that of BFU-E. These results suggest that IFN-gamma is an essential cytokine that affects human hematopoiesis and exerts a bimodal effect on stem cell maturation; potentiating or replacing the effect of early-acting cytokines such as SCF or IL-3, and suppressing the growth of matured progenitor cells.