Baier-Bitterlich G, Fuchs D, Wachter H
Institute for Medical Chemistry and Biochemistry University of Innsbruck, Austria.
Biochem Pharmacol. 1997 Mar 21;53(6):755-63. doi: 10.1016/s0006-2952(96)00651-x.
Infection with the human immunodeficiency virus (HIV) is accompanied by a decrease in CD4+ T cell numbers and the ultimate disruption of immunological functions. In sera of infected patients, elevated levels of interferon-gamma are detected, which is indicative of an activated TH1-type immune response. T-cell-derived interferon-gamma leads to the expression of various proinflammatory cytokines and enhanced macrophage capacity to secrete reactive oxygen intermediates. In addition, interferon-gamma is the major stimulator for the biosynthesis of neopterin and its reduced form, 7,8-dihydroneopterin. Neopterin is known as a sensitive immune activation marker in clinical laboratory diagnosis. Recent data implied a potential role of neopterin derivatives in oxygen free-radical-mediated processes, e.g. high concentrations of 7,8-dihydroneopterin were found to interfere with the oxidant-antioxidant balance, and may lead to apoptosis of human cells. In addition, 7,8-dihydroneopterin was found to be effective in the activation of redox-sensitive transcription factors and in the induction of HIV-1 gene expression. In this commentary, we describe our current view as to how neopterin derivatives, in concert with cytokines and reactive oxygen intermediates, may lead the way to the final destruction of the cellular immune system.
感染人类免疫缺陷病毒（HIV）会伴随着CD4+T细胞数量的减少以及免疫功能的最终破坏。在受感染患者的血清中，检测到干扰素-γ水平升高，这表明TH1型免疫反应被激活。T细胞衍生的干扰素-γ会导致多种促炎细胞因子的表达，并增强巨噬细胞分泌活性氧中间体的能力。此外，干扰素-γ是生物蝶呤及其还原形式7,8-二氢生物蝶呤生物合成的主要刺激物。生物蝶呤在临床实验室诊断中被认为是一种敏感的免疫激活标志物。最近的数据表明生物蝶呤衍生物在氧自由基介导的过程中可能发挥潜在作用，例如发现高浓度的7,8-二氢生物蝶呤会干扰氧化还原平衡，并可能导致人类细胞凋亡。此外，发现7,8-二氢生物蝶呤在激活氧化还原敏感转录因子和诱导HIV-1基因表达方面有效。在这篇评论中，我们描述了我们目前对于生物蝶呤衍生物如何与细胞因子和活性氧中间体协同作用，可能导致细胞免疫系统最终破坏的观点。
