Widner B, Wirleitner B, Baier-Bitterlich G, Weiss G, Fuchs D
Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Austria.
Arch Immunol Ther Exp (Warsz). 2000;48(4):251-8.
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.
细胞（Th1型）免疫反应在多种疾病的发病机制中起着核心作用。在Th1型免疫的免疫级联反应中，γ干扰素（IFN-γ）与其他细胞因子一样，起着关键作用。它引发一系列主要针对抗原特异性免疫反应正向调节的免疫相关反应。然而，在免疫激活的慢性状态下，系统性升高的IFN-γ不再具有抗原特异性，并与免疫缺陷的发展有关。IFN-γ还刺激人单核细胞/巨噬细胞中低分子量化合物新蝶呤的产生。因此，人体内新蝶呤的浓度反映了Th1型免疫激活的程度。由于IFN-γ还刺激免疫活性细胞释放活性氧（ROS），产生的新蝶呤量也可作为氧化应激的间接指标。同时，IFN-γ激活色氨酸的降解，这似乎限制了细胞内病原体的生长和包括T淋巴细胞在内的细胞增殖。因此，在免疫激活的持续状态下，IFN-γ的产生不仅与免疫反应的正向调节有关，还与免疫抑制机制有关。新蝶呤形成增加和色氨酸降解可能导致T细胞反应性降低和免疫缺陷的发展。
