Kynurenine pathway metabolism and immune activation: Peripheral measurements in psychiatric and co-morbid conditions
Abstract
Immune activation is inextricably linked with dysregulation of the tryptophan metabolism, shifting catabolic routes towards oxidative breakdown along the kynurenine axis. Several enzymes are able to metabolize tryptophan, but activity of inducible indoleamine 2,3-dioxygenase (IDO-1) plays a major role under pro-inflammatory, interferon-γ (IFN-γ) dominated settings. Accelerated breakdown of tryptophan into kynurenine, dysregulation of further downstream metabolism and impaired enzymatic activities due to the absence of oxidation sensitive cofactors are associated with a broad variety of primary disorders and co-morbidities. Deprivation of the essential amino acid tryptophan suppresses growth of pathogens or tumor cells but also restricts T cell proliferation, which favors immunosuppression. In addition, diminished levels of tryptophan lead to lower synthesis of neurotransmitter serotonin, this being probably the most important biochemical cause of psychiatric co-morbidities associated with a broad variety of chronic inflammatory disorders. Also other frequent co-occurring symptoms and conditions such as anemia or cachexia may be at least partially caused by the lowered levels of the essential growth factor tryptophan. Tissue and cell specific expression of kynurenine downstream processing enzymes and their defective regulation may contribute to symptom diversification. Several kynurenine downstream metabolites show potent bioactivities, thus leading to the defects in a variety…
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The microbiota may indirectly affect host kynurenine production via glucocorticoid control of liver TDO or immune-based IDO activation.
“Since the microbiota modulates host circulating glucocorticoids and their production in response to stress (Sudo et al., 2004), as well as educating the immune system, the microbiota may indirectly affect host kynurenine production via glucocorticoid control of liver TDO (Badawy, 2017;O'Farrell and Harkin, 2017) or immune-based IDO activation (Strasser et al., 2017).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Strasser et al., 2017
Cites
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“A decrease of tryptophan levels and an increase kynurenine to tryptophan ratio (Kyn/Trp) was found in several pathologies that are associated with chronic immune activation (Schroecksnadel et al., 2006), and this decrease was ascribed to inflammation-induced IDO-1 activity.”
InfluentialSelf-citationGuillemin, G. J., Smythe, G., Takikawa, O., & Brew, B. J. (2005) · Glia · doi:10.1002/glia.20090 · Cited by 497 · cited 1× · see citing works
“The further downstream metabolism of kynurenine depends on the enzymatic repertoire and differs among cell types (Werner-Felmayer et al., 1989; Guillemin et al., 2003, Guillemin et al., 2005; Chiarugi et al., 2001).”
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“The contribution of a genetic component in the development of depression was discussed, as a possible association between a genetic polymorphism in the IDO-1 gene with the risk of depression in patients treated with IFN-α was found (Galvão-de Almeida et al., 2011; Smith et al., 2012).”
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Cryan, J. F., O'Riordan, K. J., Cowan, C. S. M., Sandhu, K. V., Bastiaanssen, T. F. S., Boehme, M., Codagnone, M. G., Cussotto, S., Fulling, C., Golubeva, A. V., et al. (2019) · Physiological Reviews · doi:10.1152/physrev.00018.2018 · Cited by 5,286 · see citing works
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Role of dietary protein and muscular fitness on longevity and aging
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- Authors
- Strasser, B., Becker, K., Fuchs, D., & Gostner, J. M.
- Affiliations
- Innsbruck Medical University (AT)
- Corresponding author
- Fuchs, Dietmar
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2017-01
- Volume
- 112
- Issue
- Pt B
- Pages
- 286-296
- ISSN
- 0028-3908 (ISSN-L)
- OpenAlex
- W2273585977
- Cited by
- 97
- References
- 6
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 16 · 2023: 11 · 2022: 4 · 2021: 11 · 2020: 15 · 2019: 5 · 2018: 8 · 2017: 5 · 2016: 4
- FWCI
- 0.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Keywords
- kynurenine pathway, tryptophan metabolism, immune activation, indoleamine 2,3-dioxygenase, kynurenine/tryptophan ratio, mental illness, chronic inflammation, serotonin synthesis, interferon-gamma, immunosuppression, T cell proliferation, anemia, cachexia, biomarkers, personalized treatment
- MeSH terms
- Animals, Mental Disorders, Humans, Immune System Diseases, Kynurenine, Tryptophan, Indoleamine-Pyrrole 2,3,-Dioxygenase, Metabolic Networks and Pathways
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