Title
Neurotoxic and neuroprotective metabolites of kynurenine in patients with renal cell carcinoma treated with interferon-<tex>$\alpha$</tex>: course and relationship with psychiatric status
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Publication type
article
Publication
Tokyo ,
Subject
Human medicine
Source (journal)
Psychiatry and clinical neurosciences. - Tokyo
Volume/pages
62(2008) :5 , p. 597-602
ISSN
1323-1316
ISI
000259685000016
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Aims: Immunotherapy with interferon-á (IFN-á) is associated with psychiatric side-effects, including depression. One of the putative pathways underlying these psychiatric side-effects involves tryptophan (TRP) metabolism. Cytokines including IFN-á induce the enzyme indoleamine 2,3-dioxygenase (IDO), which converts TRP to kynurenine (KYN), leading to a shortage of serotonin (5-HT). In addition, the production of neurotoxic metabolites of KYN such as 3-hydroxykynurenine and quinolinic acid (QA) might increase and contribute to IFN-á-induced psychopathology. In contrast, other catabolites of KYN, such as kynurenic acid (KA), are thought to have neuroprotective properties. Methods: In a group of 24 patients treated with standard IFN-á for metastatic renal cell carcinoma (RCC), combined psychiatric and laboratory assessments were performed at baseline, 4 and 8 weeks, and at 6 months. Results: No psychopathology was observed, despite an increase in neurotoxic challenge as reflected in indices for the balance between neurotoxic and neuroprotective metabolites of KYN. Conclusions: The present hypothesis that a shift in the balance between neurotoxic and neuroprotective metabolites of KYN underlies the neuropsychiatric side-effects of IFN-á-based immunotherapy, is neither supported nor rejected.
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