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Modulation of neopterin formation and tryptophan degradation by Th1- and Th2-derived cytokines in human monocytic cells

1999; Oxford University Press; Volume: 116; Issue: 3 Linguagem: Inglês

10.1046/j.1365-2249.1999.00910.x

1365-2249

Günter Weiß, C. Murr, Heinz Zoller, M HAUN, Bernhard Widner, Christof Ludescher, Dietmar Fuchs,

Peroxisome Proliferator-Activated Receptors

Abstract 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 neopterin and degradation of tryptophan, two metabolic pathways induced by interferon-gamma (IFN-γ) 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 degradation were induced similarly by IFN-γ in all three cell types investigated, but the effects of interleukins were different between THP-1, primary macrophages and PBMC. In PBMC, but not in THP-1 cells and primary macrophages, IL-12 was found to be additive to the effects of IFN-γ to superinduce neopterin formation and tryptophan degradation. IL-4 and IL-10 reduced the effects of IFN-γ on monocytic cells, and both cytokines were additively antagonistic to IFN-γ in PBMC and THP-1 cells. Finally, on preincubation, but not on addition of IL-12, the effects of IL-4 and IL-10 on PBMC could be abrogated, whereas no such effect was seen in THP-1 cells. The results show that IL-12 up-regulates neopterin formation and tryptophan degradation by inducing additional IFN-γ production by Th1 cells, while a direct 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-γ effects towards monocytes/macrophages. The results clearly show how Th1 cell-mediated immunity may be up- or down-regulated by endogenous cytokine production.