ROLE OF NEOPTERIN AND 7,8-DIHYDRONEOPTERIN IN HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION - MARKER FOR DISEASE PROGRESSION AND PATHOGENIC LINK

Human immunodeficiency virus (HIV) infection is associated with increa sed concentrations of neopterin derivatives, released in large quantit ies by human macrophages on stimulation with interferon-gamma (INF-gam ma). Neopterin concentrations thus inversely correlate with absolute C D4(+) T-cell numbers and strongly predict progression of disease from latency to AIDS. Investigations of hydrogen peroxide-induced chemilumi nescence indicated a potential role of neopterin and 7,8-dihydroneopte rin in oxygen free radical-mediated processes. Indeed, 7,8-dihydroneop terin is able to enhance tumor necrosis factor alpha (TNF-alpha)-induc ed apoptosis, accompanied by an increased production of reactive oxyge n intermediates (ROIs). In line with this finding, the same combinatio n appears to contribute to the upregulation of HIV replication due to activation of nuclear factor-kappa B (NF-kappa B), a central enhancer element of the HIV LTR promoter. Thus, besides the role of neopterin a s sensitive indicator of disease activity in HIV infection, neopterin derivatives apparently are associated with the cascade of events that regulate the HIV production in infected individuals.