G. Weiss et al., Modulation of neopterin formation and tryptophan degradation by Th1-and Th2-derived cytokines in human monocytic cells, CLIN EXP IM, 116(3), 1999, pp. 435-440
In order to examine the regulatory effects of major Th1-derived cytokines,
such as IL-12, and Th2 cytokines, IL-4 and IL-10, on the formation of neopt
erin and degradation of tryptophan, two metabolic pathways induced by inter
feron-gamma (IFN-gamma) in human monocytes/macrophages, we investigated the
human monocytic cell line THP-1, primary human macrophages, and peripheral
blood mononuclear cells (PBMC). Neopterin formation and tryptophan degrada
tion were induced similarly by IFN-gamma in all three cell types investigat
ed, but the effects of interleukins were different between THP-1, primary m
acrophages and PBMC. In PBMC, but not in THP-1 cells and primary macrophage
s, IL-12 was found to be additive to the effects of IFN-gamma to superinduc
e neopterin formation and tryptophan degradation. IL-4 and IL-10 reduced th
e effects of IFN-gamma on monocytic cells, and both cytokines were additive
ly antagonistic to IFN-gamma in PBMC and THP-1 cells. Finally, on preincuba
tion, but not on addition of IL-12, the effects of IL-4 and IL-10 on PBMC c
ould be abrogated, whereas no such effect was seen in THP-1 cells. The resu
lts show that IL-12 up-regulates neopterin formation and tryptophan degrada
tion by inducing additional IFN-gamma production by Th1 cells, while a dire
ct effect of IL-12 on monocytes/macrophages appears to be absent. Similarly
, IL-4 and IL-10 inhibit neopterin production and tryptophan degradation in
PBMC by down-regulating Th1-type cytokine production and possibly also via
direct deactivation of IFN-gamma effects towards monocytes/macrophages. Th
e results clearly show how Th1 cell-mediated immunity may be up- or down-re
gulated by endogenous cytokine production.