Effects of interleukin-4 on myelopoiesis: Localization of the action of IL-4 in the CD34⁺HLA-DR⁺⁺ subset and distinction between direct and indirect effects of IL-4

We compared the myelopoietic effects of interleukin-4 (IL-4) on CD34⁺HLA-DR⁺ and on CD34⁺HLA-DR⁺⁺ bone marrow progenitor cells stimulated by either granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3). IL-4 stimulates G-CSF-induced colony-forming unit-granulocyte (CFU-G) and inhibits all colony types induced by GM-CSF and IL-3 in the HLA-DR⁺⁺ population, but not in the HLA-DR⁺ population. In CD34⁺HLA-DR⁺ cells, however, a stimulation of G-CSF-supported CFU-G was also seen with sequential application of IL-4 in liquid cultures followed by G-CSF in agar cultures. In order to confirm that these are direct effects of IL-4, single-cell culture experiments were performed with CD34⁺HLA-DR⁺⁺ cells. In these cultures IL-4 stimulates G-CSF-induced CFU-G and only inhibits colony-forming unit-macrophage (CFU-M) regardless of the CSF used to generate them.