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

Journal article

IL-12 is important for Th1 differentiation. Myeloid-derived antigen-presenting cells (APC) such as monocytes, macrophages (Mphi) 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 Mphi 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-gamma produced minimal IL-12 p70 by comparison with DC or monocytes, despite comparable production of TNF-alpha. M-CSF-induced Mphi produced low levels of IL-10 constitutively and high levels after stimulation with LPS, but neutralization of IL-10 did not augment Mphi IL-12 production. Exposure of Mphi to TNF-alpha, granulocyte-macrophage CSF or IFN-gamma did not substantially up-regulate IL-12. Therefore M-CSF induces a differentiated Mphi phenotype in which IL-12 production is down-regulated, perhaps irreversibly. This may be the default pathway for monocyte-Mphi development in the absence of inflammation.

Authors: Smith, W; Feldmann, M; Londei, M

• Publication status: Published
• Journal: European journal of immunology
• Volume: 28
• Issue: 8
• Pages: 2498-2507
• Publication date: 1998-08-01
• DOI: 10.1002/(sici)1521-4141(199808)28:08<2498::aid-immu2498>3.0.co;2-q
• EISSN: 1521-4141
• ISSN: 0014-2980
• Language: English
• Keywords: Macrophages; Humans; Interleukin-12; Dendritic Cells; Listeria monocytogenes; Cell Differentiation; Macrophage Colony-Stimulating Factor; Neutralization Tests; Interleukin-10; Monocytes; Phenotype