Effects of granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-2, interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α) and IL-6 on the production of immunoreactive IL-1 and TNF-α by human monocytes

Abstract

SUMMARY The effects of GM-CSF, IL-2, IFN-γ, TNF-α and IL-6 on the production of IL-1 (both secreted and cell associated) and TNF-α by peripheral blood monocytes were studied. Monocytes were cultured for 20 h in suspension and in serum-free conditions which minimized background stimulation of monokine production. GM-CSF, IL-2 and TNF-α directly induced the production of cell-associated IL-1 but little or no IL-1 or TNF-α secretion. Combination of GM-CSF with IFN-γ, IL-2 or TNF-α synergistically enhanced IL-1 secretion and had an additive effect on cell-associated IL-1 production. Combination of IL-2 with IFN-γ or TNF-α also synergistically enhanced IL-1 secretion but the effect on cell-associated IL-1 production was less than additive. GM-CSF synergisticaily enhanced TNF-α secretion induced by IFN-γ but not by tipopolysaccharide. GM-CSF did not enhance TNF-α secretion induced by IL-2 or TNF-α. In contrast, IL-2 synergistically enhanced TNF-α secretion induced by IFN-γ. These results are discussed in relation to cytokine involvement in rheumatoid arthritis.