Interferon‐γ and interleukin‐4 reciprocally regulate the production of monocytes/macrophages and neutrophils through a direct effect on committed monopotential bone marrow progenitor cells

Abstract

We studied the direct effects of interferon-γ (IFN-γ) in single cell colony assays of CD34⁺HLA-DR++ bone marrow progenitor cells stimulated by either granu-locyte-colony-stimulating factor (G-CSF), interleukin(IL)-3, granulocyte/macro-phage-colony-stimulating factor (GM-CSF), combinations of these CSF or medium conditioned by the 5637 human bladder carcinoma cell line. In this culture system IFN-γ stimulated monocytic colonies (CFU-M) no matter which CSF or CSF combination was used to support them and inhibited granulocytic colonies (CFU-G) if they were generated in the presence of G-CSF. IL-4 antagonized the myelopoietic effects of IFN-γ: the IFN-γ induced suppression of G-CSF-supported CFU-G, as well as the stimulation of CFU-M, were reversed by IL-4. In all cultures, IFN-γ had a limited, but statistically non-significant, inhibitory effect on CFU-GM, which was not affected by the presence of IL-4. These data show that IFN-γ and IL-4 reciprocally regulate the generation of myeloid cells involved in humoral (neutrophils) and cellular (macrophages) immune responses through a direct effect on monopotential myeloid progenitor cells.