Alpha-interferon: differential suppression of colony growth from human erythroid, myeloid, and megakaryocytic hematopoietic progenitor cells

The effect of varying concentrations of interferon-alpha (IFN-alpha) on the in vitro colony growth from all single-lineage human hematopoietic colony-forming progenitor cells was evaluated. IFN-alpha was tested at concentrations of 0, 2, 20, and 200 U/ml in optimally stimulated bone marrow cultures from each of 4 volunteer donors. Substantial donor-to-donor variability and distinct, lineage-specific patterns of stem cell sensitivity to IFN-alpha were observed. In the erythroid series, the more primitive progenitor or burst-forming unit (BFU-E) was substantially more resistant to growth inhibition at low IFN-alpha concentrations than the mature colony-forming unit (CFU-E). Colony growth by the megakaryocyte progenitor cell (CFU-Meg) was decreased by all concentrations of IFN-alpha which produced a biphasic, inhibitory dose response. The response of the colony-forming unit granulocyte/macrophage (CFU-GM) was heterogeneous among the donors tested. CFU-GM growth from 2 donors was insensitive to IFN-alpha at all concentrations. Conversely, CFU-GM from the other 2 donors manifested a steep dose-response curve that was similar to that of the CFU-E. These data demonstrate a heterogeneity of progenitor cell sensitivity to growth suppression by IFN-alpha which appears to be influenced by (i) hematopoietic lineage, (ii) degree of differentiation of the progenitor cell, and (iii) individual variability.