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Indoleamine-2, 3-dioxygenase and other interferon-gamma-mediated pathways in patients with human immunodeficiency virus infection.
Curr Drug Metab 2007; 8(3):225-36CD

Abstract

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.

Authors+Show Affiliations

Department of Internal Medicine, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. Katharina.schroecksnadel@uki.atNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

17430111

Citation

Schroecksnadel, Katharina, et al. "Indoleamine-2, 3-dioxygenase and Other Interferon-gamma-mediated Pathways in Patients With Human Immunodeficiency Virus Infection." Current Drug Metabolism, vol. 8, no. 3, 2007, pp. 225-36.
Schroecksnadel K, Zangerle R, Bellmann-Weiler R, et al. Indoleamine-2, 3-dioxygenase and other interferon-gamma-mediated pathways in patients with human immunodeficiency virus infection. Curr Drug Metab. 2007;8(3):225-36.
Schroecksnadel, K., Zangerle, R., Bellmann-Weiler, R., Garimorth, K., Weiss, G., & Fuchs, D. (2007). Indoleamine-2, 3-dioxygenase and other interferon-gamma-mediated pathways in patients with human immunodeficiency virus infection. Current Drug Metabolism, 8(3), pp. 225-36.
Schroecksnadel K, et al. Indoleamine-2, 3-dioxygenase and Other Interferon-gamma-mediated Pathways in Patients With Human Immunodeficiency Virus Infection. Curr Drug Metab. 2007;8(3):225-36. PubMed PMID: 17430111.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Indoleamine-2, 3-dioxygenase and other interferon-gamma-mediated pathways in patients with human immunodeficiency virus infection. AU - Schroecksnadel,Katharina, AU - Zangerle,R, AU - Bellmann-Weiler,R, AU - Garimorth,K, AU - Weiss,G, AU - Fuchs,Dietmer, PY - 2007/4/14/pubmed PY - 2007/5/26/medline PY - 2007/4/14/entrez SP - 225 EP - 36 JF - Current drug metabolism JO - Curr. Drug Metab. VL - 8 IS - 3 N2 - 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. SN - 1389-2002 UR - https://www.unboundmedicine.com/medline/citation/17430111/Indoleamine_2_3_dioxygenase_and_other_interferon_gamma_mediated_pathways_in_patients_with_human_immunodeficiency_virus_infection_ L2 - http://www.eurekaselect.com/58993/article DB - PRIME DP - Unbound Medicine ER -