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Cellular immune activation, neopterin production, tryptophan degradation and the development of immunodeficiency

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Cellular (Th1-type) immune response is centrally involved in the pathogenesis of various diseases. Within the immunological cascades of Th1-type immunity, interferon (IFN-), 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 drecreased T cell responsiveness and development of immunodeficiency.
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B. Widner, Institute of Medical Chemistry and Biochemistry, University of Innsbruck, A-6020 Innsbruck, Austria
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