The dual regulatory role of interleukin 4 is mediated through a direct effect on the target cell

The mechanisms responsible for regulating the growth and differentiation of pluripotent stem cells involve the complex interaction of a series of specific and nonspecific growth factors and signals. In this report, colony-stimulating factor (CSF)-dependent clonal cell lines, recombinant and/or purified CSFs, and clonal assays were used to investigate the mechanism of interleukin 4 (IL-4)-induced modulation of CSF-dependent cell growth. IL-4 inhibits in a dose-dependent fashion either the interleukin 3 (IL-3)- or granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced growth of the myelomonocytic progenitor cell line, FDC-P1. This inhibitory effect of IL-4- on IL-3- or GM-CSF-induced cell growth was verified using normal bone marrow cells. Our data supports the hypothesis that IL-4 is acting directly on the progenitor cell and not indirectly through the action of accessory cells. Further, because the inhibitory effect of IL-4 is selective and does not affect all CSF-dependent cell lines, other factors, including the maturational state or the lineage of the cell may be important in dictating an effect, if any, mediated by IL-4.