Synergistic interaction of bacterial lipopolysaccharide and the monocyte-macrophage colony-stimulating factor: potential quantitative and qualitative changes in macrophage-produced cytokine bioactivity.
In this brief definitive report, we show that over a 6-h period and under serum-free conditions, recombinant monocyte-macrophage colony-stimulating factor 1 (rCSF-1) and lipopolysaccharide (LPS) synergize and induce macrophages to express higher levels of mRNA for interleukin 1 alpha (IL-1 alpha), IL-1 beta, tumor necrosis factor alpha (TNF-alpha), and IL-6 and to release more bioactivity than macrophages treated with LPS alone. This synergy was regulated by the amount of LPS in the culture medium. Paraformaldehyde-fixed macrophages like-wise showed augmentation of IL-1 activity, but whereas all of the bioactivity associated with the fixed macrophages could be neutralized by anti-IL-1 alpha antibody only approximately 40% of the supernate activity could be attributed to IL-1 alpha. Preliminary data suggest that the augmenting effect induced by CSF-1 cannot be explained solely on a quantitative basis because the addition of rIL-1 alpha to supernates of macrophages treated with LPS alone or with the combination of LPS and CSF-1 resulted in an increase in thymocyte mitogenic activity to a level that could not be explained on an additive basis. Although the supernates contained TNF and IL-6, antibody neutralization assays made it unlikely that these were directly responsible for the augmenting effect. These results suggest that CSF-1 not only enhances basic genetic responses induced by LPS alone but also may induce a mechanism that amplifies cytokine bioactivity.
Evans
R
R
Jackson Laboratory, Bar Harbor, ME 04609.
Kamdar
S J
SJ
Duffy
T M
TM
Fuller
J
J
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D004357:Drug Synergism; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D008070:Lipopolysaccharides / Q000502:physiology*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D012313:RNA / Q000235:genetics; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism / Q000502:physiology
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D012313:RNA; D016173:Macrophage Colony-Stimulating Factor