Title
Neurotoxic and neuroprotective metabolites of kynurenine in patients with renal cell carcinoma treated with interferon-<tex>$\alpha$</tex>: course and relationship with psychiatric statusNeurotoxic 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
Research group
Department of Pharmaceutical Sciences
Medical Biochemistry
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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