Contrasting effects of interferon-gamma and interleukin-4 on neopterin generation from human adherent monocytes

The production of neopterin is closely correlated with activation of cell-mediated immunity. Neopterin appears to be produced by human macrophages specifically stimulated with interferon-gamma (IFN-gamma). Interleukin-4 (IL-4), a B and T stimulatory factor, has recently been shown to inhibit monocyte/macrophage functions, including the ability to suppress monocyte-generated cytokines. In this report we confirmed previous studies that identified the monocyte/macrophage as the main producing cell among human blood cells and that secretion is stimulated by IFN-gamma and lipopolysaccharides (LPS). IL-4 inhibits the generation of neopterin from unstimulated monocytes. This inhibitory effect was dose dependent and occurred at concentrations lower than 0.01 ng/ml. However, IL-4 had only a minimal inhibitory effect on LPS-induced generation of neopterin and could not reverse IFN-gamma-induced neopterin secretion from adherent monocytes. Furthermore, we report that LPS induced IFN-gamma production in monocyte culture. This production is strongly inhibited by IL-4 treatment. These findings indicate that IL-4 can regulate the synthesis of neopterin by adherent blood mononuclear cells and provide further evidence that LPS-induced neopterin in macrophages may act by IFN-gamma-independent mechanisms.