Effect of Interleukin-4 on the Growth of Granulocyte-Macrophage Progenitor Cells Stimulated by Hematopoietic Growth Factors

Abstract

The effects of recombinant murine interleukin-4 (rmIL-4) on murine granulocyte-macrophage progenitor cells (CFU-GM) were investigated in the presence or absence of recombinant human granulocyte colony stimulating factor (rhG-CSF), recombinant murine granulocyte-macrophage colony stimulating factor (rmGM-CSF) or recombinant murine interleukin-3 (rmIL-3) both in serum-free and serum-containing cultures. IL-4 alone could not support any CFU-GM colony formation in both culture systems. In serum-free cultures, IL-4 inhibited CFU-GM colony formation stimulated by G-CSF, GM-CSF or IL-3 from whole bone marrow cells (whole BM cells), nonadherent, nonphagocytic and T cell-depleted BM cells (fractionated BM cells) or whole BM cells of 5-Fluorouracil (5-FU) treated mice. On the other hand, in serum-containing cultures, IL-4 inhibited CFU-GM colony formation stimulated by GM-CSF or IL-3, but IL-4 dose-dependently enhanced G-CSF-stimulated colony formation from both whole and fractionated BM cells. Morphological examinations revealed that IL-4 predominantly inhibited granulocyte-lineage colony formation stimulated by GM-CSF or IL-3 in both culture systems. When combined with G-CSF, IL-4 predominantly inhibited granulocyte-lineage colony formation and relatively increased macrophage-lineage colonies, but in serum-containing culture, IL-4 significantly increased macrophage-lineage colony formation. The results of the present study suggest that IL-4 has an inhibitory effect on the factors (G-CSF, GM-CSF, IL-3)-dependent CFU-GM colony formation in serum-free condition and enhances only G-CSF-stimulated CFU-GM colony formation in serum-containing condition.