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Interferon gama induced Tryptophan Degradation Neuropsychiatric and Immunological Consequences

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Tryptophan is a constituent of proteins and in parallel it represents a source for mainly two pivotal biochemical pathways the generation of 5-hydroxytryptamine (serotonin), and the formation of kynurenine by the enzymes tryptophan pyrrolase (TP) and indoleamine 2,3-dioxygenase (IDO). IDO is induced by interferon-g (IFN-g ) in a broad variety of cells. Therefore, enhanced tryptophan degradation is observed in diseases and disorders concomitant with cellular immune activation, e.g. infectious diseases, autoimmune diseases, malignant diseases as well as in pregnancy. IFN-g -derived tryptophan degradation may represent an effector mechanism within in the comprehensive network of immune stimulation. In addition, the cytostatic and, respectively, antiproliferative properties on e.g., T-lymphocytes may contribute to the immunomodulatory function of IFN-g . However, especially in states of persistent immune activation increased tryptophan catabolism leads to the depletion of free serum tryptophan and to the accumulation of neuroactive kynurenine metabolites. As a consequence, serotonergic functions may be affected, and the neurotoxic properties of kynurenine derivatives may lead to neuronal disorders evoking neurological/psychiatric symptoms. This notion provides a basis for the better understanding of mood disorders and related syptoms in chronic diseases. Moreover, IDO could represent a link between the immunological network and neuroendocrine functions with far reaching consequences regarding to the psychological status of patients.
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Keywords: hydroxytryptamine; immune activatio; immunosuppressive; interferon; kynurenine derivatives; major depression; tryptophane pyrrolase

Document Type: Review Article

Publication date: September 1, 2000

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  • Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism and disposition. The journal serves as an international forum for the publication of timely reviews in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments. The journal covers the following areas:

    In vitro systems including CYP-450; enzyme induction and inhibition; drug-drug interactions and enzyme kinetics; pharmacokinetics, toxicokinetics, species scaling and extrapolations; P-glycoprotein and transport carriers; target organ toxicity and interindividual variability; drug metabolism and disposition studies; extrahepatic metabolism; phase I and phase II metabolism; recent developments for the identification of drug metabolites and adducts.
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