Van Gool Arthur R, Verkerk Robert, Fekkes Durk, Bannink Marjolein, Sleijfer Stefan, Kruit Wim H J, van der Holt Bronno, Scharpé Simon, Eggermont Alexander M M, Stoter Gerrit, Hengeveld Michiel W
Department of Psychiatry, Erasmus MC, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
Psychiatry Clin Neurosci. 2008 Oct;62(5):597-602. doi: 10.1111/j.1440-1819.2008.01854.x.
Immunotherapy with interferon-alpha (IFN-alpha) 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-alpha 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-alpha-induced psychopathology. In contrast, other catabolites of KYN, such as kynurenic acid (KA), are thought to have neuroprotective properties.
In a group of 24 patients treated with standard IFN-alpha for metastatic renal cell carcinoma (RCC), combined psychiatric and laboratory assessments were performed at baseline, 4 and 8 weeks, and at 6 months.
No psychopathology was observed, despite an increase in neurotoxic challenge as reflected in indices for the balance between neurotoxic and neuroprotective metabolites of KYN.
The present hypothesis that a shift in the balance between neurotoxic and neuroprotective metabolites of KYN underlies the neuropsychiatric side-effects of IFN-alpha-based immunotherapy, is neither supported nor rejected.
使用α-干扰素（IFN-α）进行免疫治疗会引发包括抑郁症在内的精神副作用。这些精神副作用潜在的途径之一涉及色氨酸（TRP）代谢。包括IFN-α在内的细胞因子会诱导吲哚胺2,3-双加氧酶（IDO），该酶将TRP转化为犬尿氨酸（KYN），导致血清素（5-HT）短缺。此外，KYN的神经毒性代谢产物如3-羟基犬尿氨酸和喹啉酸（QA）的产生可能会增加，并导致IFN-α诱导的精神病理学。相比之下，KYN的其他分解代谢产物，如犬尿喹啉酸（KA），被认为具有神经保护特性。
在一组24例接受标准IFN-α治疗转移性肾细胞癌（RCC）的患者中，在基线、4周、8周和6个月时进行了精神和实验室联合评估。
尽管KYN的神经毒性和神经保护代谢产物之间平衡的指标反映出神经毒性挑战增加，但未观察到精神病理学现象。
目前关于KYN的神经毒性和神经保护代谢产物之间平衡的变化是基于IFN-α的免疫治疗神经精神副作用基础的假设，既未得到支持也未被否定。
