SYNERGISM OF GLUCOCORTICOIDS WITH GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR (GM-CSF) BUT NOT INTERFERON-GAMMA (IFN-GAMMA) OR INTERLEUKIN-4 (IL-4) ON INDUCTION OF HLA CLASS-II EXPRESSION ON HUMAN MONOCYTES

Peripheral blood monocytes from up to 13 normal donors were stimulated with the cytokines interferon γ (IFN-γ), interleukin 4 (IL-4) and granulocyte macrophage-colony stimulating factor (GM-CSF) in the presence or absence of dexamethasone (Dex), and the effects on HLA class II (HLA-DR, DP and DQ) expression studied. Dex markedly augmented HLA-DR, DP and DQ levels induced by GM-CSF, in all samples tested. Particularly striking were the effects on HLA-DQ expression, since stimulation with a combination of Dex and GM-CSF induced markedly higher levels of HLA-DQ antigen than stimulation with IFN-γ. Northern blot analysis of samples treated for 40 hours with Dex and GM-CSF indicated that levels of DRα, DPα and DQα mRNA were also increased. In contrast, despite variation between individual donors, in general Dex weakly inhibited both constitutive and IFN-γ- or IL-4-induced HLA-DR expression. Variability in the responsiveness of monocytes purified from individual donors to each cytokine was also observed. GM-CSF was less potent than IFN-γ and IL-4, enhancing HLA class II expression in only seven of 13 donors tested, whereas in the presence of Dex all donors responded to GM-CSF. The differential effects of glucocorticoids in vitro suggest that these cytokines induce HLA class II expression by different mechanisms. © 1992.