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

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.