Human macrophages induced in vitro by macrophage colony-stimulating factor are deficient in IL-12 production

Abstract

IL-12 is important for Th1 differentiation. Myeloid-derived antigen-presenting cells (APC) such as monocytes, macrophages (MΦ) and dendritic cells (DC) are believed to be major sources of IL-12 in vivo. We have compared IL-12 production of fresh monocytes with MΦ differentiated in vitro using macrophage colony-stimulating factor (M-CSF) or human plasma, and in vitro generated dendritic cells, since these differentiated cell types represent APC at sites of antigen challenge. Macrophages stimulated with lipopolysaccharide (LPS) or heat-killed Listeria monocytogenes in the presence or absence of IFN-γ produced minimal IL-12p70 by comparison with DC or monocytes, despite comparable production of TNF-α. M-CSF-induced MΦ produced low levels of IL-10 constitutively and high levels after stimulation with LPS, but neutralization of IL-10 did not augment MΦ IL-12 production. Exposure of MΦ to TNF-α, granulocyte-macrophage CSF or IFN-γ did not substantially up-regulate IL-12. Therefore M-CSF induces a differentiated MΦ phenotype in which IL-12 production is down-regulated, perhaps irreversibly. This may be the default pathway for monocyte-MΦ development in the absence of inflammation.