Evidence that granulocyte/macrophage-colony-stimulating factor and interferon-gamma maintain the viability of human peripheral blood monocytes in part by their suppression of IL-10 production.
Prolonged culture of human peripheral blood monocytes hPBMs requires the addition of both granulocyte/macrophage-colony-stimulating factor (GM-CSF) and interferon (IFN)-gamma. Cultured hPMBs challenged with lipopolysaccharide produced large amounts of several cytokines but very little interleukin (IL)-10. However, when GM-CSF and IFN-gamma 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-gamma, there was no loss in cell number. In contrast, when IL-10 was added to cultures in the absence of GM-CSF and IFN-gamma, 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-gamma, 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-gamma are omitted from 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-gamma and protection from apoptosis by these additives.
Bach
M K
MK
Upjohn Laboratories, Kalamazoo, MI 49001, USA.
Brashler
J R
JR
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D003864:Depression, Chemical; D005786:Gene Expression Regulation / Q000187:drug effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016753:Interleukin-10 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor