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

Clin Exp Immunol. 1999 Jun;116(3):435-40. doi: 10.1046/j.1365-2249.1999.00910.x.


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-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 degradation were induced similarly by IFN-gamma 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-gamma to superinduce neopterin formation and tryptophan degradation. IL-4 and IL-10 reduced the effects of IFN-gamma on monocytic cells, and both cytokines were additively antagonistic to IFN-gamma 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-gamma 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-gamma effects towards monocytes/macrophages. The results clearly show how Th1 cell-mediated immunity may be up- or down-regulated by endogenous cytokine production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cytokines / biosynthesis
  • Cytokines / pharmacology*
  • Humans
  • In Vitro Techniques
  • Interferon-gamma / pharmacology
  • Interleukin-10 / pharmacology
  • Interleukin-12 / pharmacology
  • Interleukin-4 / pharmacology
  • Monocytes / drug effects
  • Monocytes / immunology*
  • Monocytes / metabolism*
  • Neopterin / biosynthesis*
  • Recombinant Proteins
  • Th1 Cells / immunology
  • Th2 Cells / immunology
  • Tryptophan / metabolism*


  • Cytokines
  • Recombinant Proteins
  • Interleukin-10
  • Interleukin-12
  • Interleukin-4
  • Neopterin
  • Interferon-gamma
  • Tryptophan