Cellular immune activation, neopterin production, tryptophan degradation and the development of immunodeficiency.
Cellular (Th1-type) immune response is centrally involved in the pathogenesis of various diseases. Within the immunological cascades of Th1-type immunity, interferon gamma (IFN-gamma), among other cytokines, is critically involved. It triggers a series of immune-relevant reactions mostly directed towards forward regulation of the antigen specific immune response. However, in chronic states of immune activation, systemically increased IFN-gamma is no longer antigen specific and is associated with the development of immunodeficiency. IFN-gamma also stimulates the production of neopterin, a low-mass compound, in human monocytes/macrophages. Accordingly, neopterin concentrations in humans reflect the degree of Th1-type immune activation. Since IFN-gamma also stimulates the release of reactive oxygen species (ROS) from immunocompetents cells, the amount of neopterin produced also serves as an indirect estimate of oxidative stress. In parallel, IFN-gamma activates the degradation of tryptophan, which appears to limit the growth of intracellular pathogens and the proliferation of cells, including T lymphocytes. Thus, during persisting states of immune activation, the production of IFN-gamma is not only associated with forward regulation of the immune response, but also with immunosuppressive mechanisms. The increased formation of neopterin and degradation of tryptophan may result in a decreased T cell responsiveness and development of immunodeficiency.
Widner
B
B
Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Austria.
Wirleitner
B
B
Baier-Bitterlich
G
G
Weiss
G
G
Fuchs
D
D
D006801:Humans; D007108:Immune Tolerance; D007153:Immunologic Deficiency Syndromes / Q000209:etiology*; D007371:Interferon-gamma / Q000276:immunology; D008213:Lymphocyte Activation / Q000502:physiology*; D019798:Neopterin / Q000096:biosynthesis*; D016897:Respiratory Burst; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014364:Tryptophan / Q000378:metabolism*
D019798:Neopterin; D007371:Interferon-gamma; D014364:Tryptophan