Evidence that Granulocyte/Macrophage-Colony-Stimulating Factor and Interferon-γ Maintain the Viability of Human Peripheral Blood Monocytes in Part by Their Suppression of IL-10 Production

Abstract

Prolonged culture of human peripheral blood monocytes hPBMs requires the addition of both granulocyte/macrophage-colony-stimulating factor (GM-CSF) and interferon (IFN)-γ. Cultured hPMBs challenged with lipopolysaccharide produced large amounts of several cytokines but very little interleukin (IL)-10. However, when GM-CSF and IFN-γ were omitted from the cultures, IL-10 production was readily demonstrated. Addition of IL-10 to the cultures potently inhibited the production of several cytokines and, in the presence of GM-CSF and IFN-γ, there was no loss in cell number. In contrast, when IL-10 was added to cultures in the absence of GM-CSF and IFN-γ, there was an accelerated loss of viable cells. A monoclonal antibody to IL-10, which had no effect on cell survival in the presence of GM-CSF and IFN-γ, partly prevented the loss of cells which occurred in the absence of IL-10 and these additives. Preliminary studies suggest that inclusion of anti-IL-10 can partly prevent the apoptosis which occurs when GM-CSF and IFN-γ are omitted form the cultures. These observations suggest that there is a cause and effect relationship between the failure of hPBMs to produce IL-10 when they are cultured in the presence of GM-CSF and IFN-γ and protection from apoptosis by these additives.