CHRONIC IMMUNE STIMULATION, OXIDATIVE STRESS, AND APOPTOSIS IN HIV-INFECTION

Infection with the human immunodeficiency virus (HIV) is accompanied b y a decrease in CD4(+) T cell numbers and the ultimate disruption of i mmunological 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 macropha ge capacity to secrete reactive oxygen intermediates. In addition, int erferon-gamma is the major stimulator for the biosynthesis of neopteri n and its reduced form, 7,8-dihydroneopterin. Neopterin is known as a sensitive immune activation marker in clinical laboratory diagnosis. R ecent data implied a potential role of neopterin derivatives in oxygen free-radical-mediated processes, e.g. high concentrations of 7,8-dihy droneopterin were found to interfere with the oxidant-antioxidant bala nce, and may lead to apoptosis of human cells. In addition, 7,8-dihydr oneopterin was found to be effective in the activation of redox-sensit ive transcription factors and in the induction of HIV-1 gene expressio n. In this commentary, we describe our current view as to how neopteri n derivatives, in concert with cytokines and reactive oxygen intermedi ates, may lead the way to the final destruction of the cellular immune system. (C) 1997 Elsevier Science Inc.