Control of major histocompatibility complex class II expression on human monocytes by interleukin-4: Regulatory effect of lipopolysaccharide

Interleukin-4 (IL-4), like interferon-γ (IFN-γ), stimulates monocyte major histocompatibility complex (MHC) class II expression and thus, by increasing antigen presentation, has the potential to increase immune reactivity. In this study, activation of human monocytes by lipopolysaccharide (LPS) prevented concomitant IL-4 stimulation of MHC class II expression. However, this was not a general observation for activated monocytes because although the high levels of MHC class II antigen expressed by monocytes stimulated in vitro with IFN-γ were not further regulated by IL-4, the stimulatory effects of IL-4 persisted on cells activated with granulocyte-macrophage colony stimulating factor and tumour necrosis factor-α for enhanced MHC class II expression. MHC class II expression by monocytes cultured for 7 days with macrophage colony-stimulating factor was regulated by IL-4 and LPS in a manner very similar to that detected for freshly isolated monocytes. The inhibitory effect of LPS was not due to LPS-induced production of IL-10 or regulatory prostanoids. Furthermore, IFN-γ-increased MHC class II expression was suppressed by LPS, suggesting that the regulation was at the level of MHC class II expression per se. This study suggests that during Gram-negative bacterial infections, IL-4 and IFN-γ may not be able to signal enhanced MHC class II expression and thus, enhanced immune reactivity.