human peripheral blood monocyte/macrophages and modulation of cytokine response during differentiation

Abstract: We previously reported that in vitro culture of human peripheral blood monocytes resulted in a time-dependent differentiation into macrophages and in an enhanced capacity for producing certain cytokines (i.e., tumor necrosis factor a, interleukin-6 (IL-6), and interferon-n (IFN-)1 in response to bacterial lipopoly-saccharide (LPS). lilY-i infection or gpl2O treatment of monocyte/macrophages resulted in the induction of low levels of IFN-3, which were very effective in restricting viral replication in 7-day cultured macro-phages but not in freshly isolated cells. This enhanced response of macrophages was due to a higher sensi-tivity ofthese cells to the antiviral effect ofIFN43. Con-sistent with this finding, 7-day cultured macrophages exhibited higher levels of type I IFN receptors than i-day cultured monocytes. Treatment of monocyte/ macrophages with gpl2O also caused a marked in-crease in IL-lO secretion, regardless of the differen-tiation state. No IL-12 secretion was detected in mono-cyte/macrophage cultures treated with gpl2O alone. However, consistent IL-12 secretion was found in 7-day cultured macrophages primed with IFN43 and sub-sequently stimulated with gpl2O. Macrophages re-sponded more efficiently than monocytes to the prim-ing effect of IFN43 for IL-12 production. This was consistent with a stronger antiviral response against vesicular stomatitis virus by these cells as well as with a higher expression of IFN-3 receptors. The finding that the acquisition of the macrophage phenotype is associated with an increased capacity to respond to environmental signals (such as type I and type II IFNs) underlines the importance of the differentiation pro-cess for the selection of a certain repertoire of re. sponses that may allow these cells to have importan