Human immunodeficiency virus type 1 (
HIV) infection is characterized by progressive immunodeficiency despite of an overwhelming cellular immune activation. Patients show highly elevated serum/plasma concentrations of the proinflammatory
cytokine interferon-gamma (IFN-gamma), which induces human monocytes to form
neopterin, to produce
reactive oxygen species (ROS) and in parallel, to degrade
tryptophan. Enhanced
tryptophan degradation by the
enzyme indoleamine-2, 3-dioxygenase (IDO) contributes importantly to
disease progression and "complications" of
HIV infection: By a subsequent impairment of
protein metabolism and
serotonin formation, the development of neuropsychiatric disorders and
weight loss in HIV infected patients can be enforced. Furthermore, increased IDO-activation efficiently suppresses the growth and proliferation of pathogens as well as host T-cells. IDO and other IFN-gamma-mediated pathways are strongly induced in patients with
HIV infection and are also linked with
disease progression:
Neopterin formation by
GTP-cyclohydrolase I sensitively reflects the stage of the disease, and determination of the
pteridine in body fluids is useful to monitor the efficacy of antiretroviral
therapy.
Neopterin is an independent prognostic factor for the outcome of disease, and well suited to estimate the degree of immune activation in vivo and the responsiveness of immunocompetent cells to stimulation in vitro. ROS formation may contribute to the development of oxidative stress in
HIV infection, resulting in depletion of
antioxidants. The cause-effective role of an overwhelming Th1-type immune response together with the activation of IDO and other IFN-gamma-mediated biochemical pathways for the course of
HIV infection, the development of immunodeficiency,
anemia and
weight loss in HIV patients is discussed.