A. Moutabarrik et al., CONTRASTING EFFECTS OF INTERFERON-GAMMA AND INTERLEUKIN-4 ON NEOPTERIN GENERATION FROM HUMAN ADHERENT MONOCYTES, Lymphokine and cytokine research, 11(6), 1992, pp. 327-330
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.