Sustained elevation of kynurenic Acid in the cerebrospinal fluid of patients with herpes simplex virus type 1 encephalitis
Open accessAbstract
Herpes simplex virus (HSV) type 1 encephalitis (HSE) is a viral infectious disease with commonly occurring neurodegeneration and neurological/cognitive long-term sequelae. Kynurenic acid (KYNA) is a neuroactive tryptophan metabolite, which is elevated in the cerebrospinal fluid (CSF) during viral infection as a result of immune activation. The aim of the study was to investigate the role of endogenous brain KYNA for the long-term outcome of the disease. CSF KYNA concentration was analyzed in 25 HSE patients along the course of the disease and compared with that of 25 age-matched healthy volunteers. Within 3 weeks of admission CSF KYNA of HSE patients was markedly elevated (median 33.6 nM) compared to healthy volunteers (median 1.45 nM). Following a decline observed after 1–2 months, levels of CSF KYNA were elevated more than 1 year after admission (median 3.4 nM range: 1–9 years). A negative correlation was found between initial CSF KYNA concentrations and severity of the long-term sequelae. This study show a marked elevation in CSF KYNA from patients with HSE, most pronounced during the acute phase of the disease and slowly declining along the recovery. We propose that brain KYNA might potentially protect against neurodegeneration while causing a long-lasting loss in cognitive function associated with the disease.
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Several viral infections, including HIV, HCV, and HSV, increase activation of the kynurenine pathway, which is implicated in the neurological and cognitive impairments of patients with HIV, HCV, and HSV.
“Several viral infections, including HIV [19], HCV [20], and HSV [21] increase activation of the KP, which interestingly is implicated in the neurological and cognitive impairments of patients with HIV, HCV, and HSV [21,22].”
From VEEV TC-83 Triggers Dysregulation of the Tryptophan–Kynurenine Pathway in the Central Nervous System That Correlates with Cognitive Impairment in Tg2576 Mice (2024) · cites this paper as [21]
The Discussion reports elevated cerebrospinal-fluid kynurenic acid in herpes simplex encephalitis and describes activation of the kynurenine pathway in that condition. It also suggests that kynurenic acid may contribute to cognitive deficits after herpes simplex encephalitis and HIV-1 encephalitis. The paper does not address HCV-related cognitive impairment; the separate HCV activation claim is cited to another source. (LLM, conf=0.84)
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“This is consistent with the findings of Atlas et al. (49), as both studies demonstrated a significant association of the tryptophan-kynurenine pathway in HSE.”
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Polyák, H., Galla, Z., Martos, D., Rajda, C., Monostori, P. B., Klivènyi, P., & Vécsei, L. (2026) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2026.111795
Cerebrospinal fluid, neuroinflammation, and electrospray ionization mass spectrometry
Turner, C. (2021) · Developmental Medicine & Child Neurology · doi:10.1111/dmcn.14824
“IDO activation in inflammation, in the central nervous system (CNS) as well as peripherally, is not new.(2,3) Most publications have measured kynurenine, kynurenic acid, or the kynurenine:tryptophan ratio as measures of IDO activation.”
BackgroundBrundin, L. (2016) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12544 · Cited by 1 · see citing works
- Authors
- Atlas, A., Franzen-Röhl, E., Söderlund, J., Jönsson, E. G., Samuelsson, M., Schwieler, L., Sköldenberg, B., & Engberg, G.
- Affiliations
- Karolinska University Hospital (SE)
- Infectious Diseases Unit, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden.
- Karolinska Institutet (SE)
- Linköping University (SE)
- Corresponding author
- Engberg, Göran
- Venue
- International Journal of Tryptophan Research
- Publisher
- SAGE Publications
- Published
- 2013-01
- Volume
- 6
- Pages
- 89-96
- ISSN
- 1178-6469 (ISSN-L)
- PMC
- PMC3855257
- OpenAlex
- W2028047260
- Cited by
- 25
- References
- 69
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2022: 2 · 2021: 6 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 3 · 2014: 2
- FWCI
- 0.75
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- International Journal of Tryptophan Research (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Epidemiology › Herpesvirus Infections and Treatments
- Health Sciences › Medicine › Infectious Diseases › Infectious Encephalopathies and Encephalitis
- Keywords
- kynurenic acid, herpes simplex virus type 1 encephalitis, cerebrospinal fluid, tryptophan metabolism, neurodegeneration, long-term sequelae, cognitive impairment, neuroprotection, immune activation, viral encephalitis
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