Potential role of immune system activation-associated production of neopterin derivatives in humans

Neopterin derivatives are produced by human monocyte-derived macrophages and dendritic cells upon stimulation with interferons. Neopterin concentrations measured in urine or blood reflect activation of cellular immunity and endogenous release of interferon-gamma. This review focuses on the clinical utility of measuring neopterin levels in inflammatory disease and the potential functions of neopterin as a mediator and/or modulator in the course of inflammatory and infectious processes. In vitro-studies revealed that neopterin derivatives exhibit distinct biochemical effects, most likely via interactions with reactive oxygen or nitrogen intermediates, thereby affecting the cellular redox state. Data support the hypothesis that the release of neopterin enhances the cytotoxic potential of activated macrophages and dendritic cells. In vivo, a strong correlation between neopterin levels and the severity, progression, and outcome of infectious and inflammatory diseases was found. The influence of neopterin derivatives on the cellular metabolism may provide an explanation for these clinical observations.