Neurotoxic and neuroprotective metabolites of kynurenine in patients with renal cell carcinoma treated with interferon-α: Course and relationship with psychiatric status
Aims: Immunotherapy with interferon-α (IFN-α) 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-α 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-α-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-α 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-α-based immunotherapy, is neither supported nor rejected.
|Keywords||3-hydroxykynurenine, Depression, Interferon-α, Kynurenic acid, Kynurenine, Neurotoxicity, Quinolinic acid|
|Persistent URL||dx.doi.org/10.1111/j.1440-1819.2008.01854.x, hdl.handle.net/1765/30239|
|Journal||Psychiatry and Clinical Neurosciences|
van Gool, A.R, Verkerk, R, Fekkes, D, Bannink, M, Sleijfer, S, Kruit, W.H.J, … Hengeveld, M.W. (2008). Neurotoxic and neuroprotective metabolites of kynurenine in patients with renal cell carcinoma treated with interferon-α: Course and relationship with psychiatric status. Psychiatry and Clinical Neurosciences, 62(5), 597–602. doi:10.1111/j.1440-1819.2008.01854.x