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 c ell-mediated immunity. Neopterin appears to be produced by human macro phages specifically stimulated with interferon-gamma (IFN-gamma). Inte rleukin-4 (IL-4), a B and T stimulatory factor, has recently been show n to inhibit monocyte/macrophage functions, including the ability to s uppress monocyte-generated cytokines. In this report we confirmed prev ious studies that identified the monocyte/macrophage as the main produ cing 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 d ose dependent and occurred at concentrations lower than 0.01 ng/ml. Ho wever, IL-4 had only a minimal inhibitory effect on LPS-induced genera tion of neopterin and could not reverse IFN-gamma-induced neopterin se cretion from adherent monocytes. Furthermore, we report that LPS induc ed IFN-gamma production in monocyte culture. This production is strong ly inhibited by IL-4 treatment. These findings indicate that IL-4 can regulate the synthesis of neopterin by adherent blood mononuclear cell s and provide further evidence that LPS-induced neopterin in macrophag es may act by IFN-gamma-independent mechanisms.