EFFECTS OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR (GM-CSF), IL-2, INTERFERON-GAMMA (IFN-GAMMA), TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA) AND IL-6 ON THE PRODUCTION OF IMMUNOREACTIVE IL-1 AND TNF-ALPHA BY HUMAN MONOCYTES

The effects of GM-CSF, IL-2, IFN-gamma, TNF-alpha and IL-6 on the production of IL-1 (both secreted and cell associated) and TNF-alpha 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-alpha-directly induced the production of cell-associated IL-1 but little or no IL-1 or TNF-alpha-secretion. Combination of GM-CSF with IFN-gamma, IL-2 or TNF-alpha-synergistically enhanced IL-1 secretion and had an additive effect on cell-associated IL-1 production. Combination of IL-2 with IFN-gamma or TNF-alpha also synergistically enhanced IL-1 secretion but the effect on cell-associated IL-1 production was less than additive. GM-CSF synergistically enhanced TNF-alpha-secretion induced by IFN-gamma but not by lipopolysaccharide. GM-CSF did not enhance TNF-alpha-secretion induced by IL-2 or TNF-alpha. In contrast, IL-2 synergistically enhanced TNF-alpha-secretion induced by IFN-gamma. These results are discussed in relation to cytokine involvement in rheumatoid arthritis.