title: Neopterin production, tryptophan degradation, and mental depression--what is the link?
abstract: The cytokine interferon-gamma stimulates human monocytes/macrophages to release large amounts of neopterin. Increased neopterin concentrations in body fluids of patients are observed during diseases with activated cellular (=TH1-type) immune response such as allograft rejection, virus infections, autoimmune disorders, or malignant tumors but also in neurodegenerative diseases or during pregnancy. In various cells interferon-gamma induces indoleamine 2,3-dioxygenase (IDO) which degrades tryptophan via the kynurenine pathway. Therefore like increased neopterin formation, enhanced tryptophan degradation is observed in diseases concomitant with cellular immune activation. Disturbed metabolism of tryptophan affects biosynthesis of neurotransmitter 5-hydroxytryptamine (serotonin), and it appears to be associated with an increased susceptibility for depression. In fact, enhanced neopterin concentrations together with increased degradation of tryptophan and low serum levels of tryptophan correlate with neuropsychiatric abnormalities like cognitive decline and depressive symptoms especially in long-lasting and chronic diseases. Activation of IDO could represent an important link between the immunological network and the pathogenesis of depression.
authors.affiliation: Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Fritz Pregl Strasse 3, Innsbruck A-6020, Austria.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Widner
authors.forename: Andreas
authors.initials: A
authors.lastname: Laich
authors.forename: Barbara
authors.initials: B
authors.lastname: Sperner-Unterweger
authors.forename: Maximilian
authors.initials: M
authors.lastname: Ledochowski
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs
mesh_terms: D003866:Depressive Disorder / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma / Q000378:metabolism; D019798:Neopterin / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism*; D014366:Tryptophan Oxygenase / Q000378:metabolism*
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D012701:Serotonin; D019798:Neopterin; D007371:Interferon-gamma; D014364:Tryptophan; D014366:Tryptophan Oxygenase