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dc.contributor.authorQuist-Paulsen, Elseen_US
dc.contributor.authorAukrust, Pålen_US
dc.contributor.authorKran, Anne-Marte Bakkenen_US
dc.contributor.authorDunlop, Oona Borghilden_US
dc.contributor.authorOrmaasen, Vidaren_US
dc.contributor.authorStiksrud, Birgitteen_US
dc.contributor.authorMidttun, Øivinden_US
dc.contributor.authorUeland, Thoren_US
dc.contributor.authorUeland, Per Magneen_US
dc.contributor.authorMollnes, Tom Eiriken_US
dc.contributor.authorDyrhol-Riise, Anne Maen_US
dc.PublishedQuist-Paulsen EL, Aukrust P, Kran A, Dunlop OB, Ormaasen V, Stiksrud B, Midttun Ø, Ueland T, Ueland PM, Mollnes TE, Dyrhol-Riise AM. High neopterin and IP-10 levels in cerebrospinal fluid are associated with neurotoxic tryptophan metabolites in acute central nervous system infections. Journal of Neuroinflammation. 2018;15(327)eng
dc.description.abstractBackground The host response to intruders in the central nervous system (CNS) may be beneficial but could also be harmful and responsible for neurologic symptoms and sequelae in CNS infections. This immune response induces the activation of the kynurenine pathway (KP) with the production of neuroactive metabolites. Herein, we explored cytokine and KP responses in cerebrospinal fluid (CSF) and serum in patients with encephalitis, aseptic, and bacterial meningitis. Methods Cytokines were measured in CSF and serum by multiplex assay in adult patients with encephalitis of infectious, autoimmune or unknown etiology (n = 10), aseptic meningitis (ASM, n = 25), acute bacterial meningitis (ABM, n = 6), and disease control patients with similar symptoms but without pleocytosis in CSF (n = 42). Liquid chromatography-tandem mass spectrometry (LC-MS/ MS) was used to measure KP metabolites in CSF and serum. Results A characteristic pattern of increasing cytokine levels and KP metabolites was found in CSF from encephalitis to ASM, with the highest levels in ABM. In ASM and ABM, most inflammatory mediators, including IL-6, IL-8, and IFN-inducible protein-10 (IP-10), showed markedly elevated levels in CSF compared with serum, indicating production within the CNS. In contrast to most mediators, the highest level of IP-10 was found in the ASM group, suggesting a potential role for IP-10 in aseptic/viral meningitis. Neopterin and IP-10 were associated with marked changes in KP metabolites in CSF with increasing kynurenine/tryptophan ratio reflecting indoleamine 2,3-dioxygenase activity. Neopterin, a marker of IFN-γ activity, was associated with an unfavorable balance between neuroprotective and neurotoxic tryptophan metabolites. Conclusion We show that parenchymal and meningeal inflammations in CNS share a characteristic cytokine profile with a general immune response in the CSF with limited influence from the systemic circulation. IFN-γ activity, assessed by neopterin and IP-10 levels, may play a role in the activation of the KP pathway in these patients, potentially mediating neurotoxic effects.en_US
dc.publisherSpringer Natureeng
dc.rightsAttribution CC BYeng
dc.subjectAseptic meningitiseng
dc.subjectBacterial meningitiseng
dc.subjectKynurenine tryptophan pathwayeng
dc.subjectIndoleamine 2,3-dioxygenaseeng
dc.titleHigh neopterin and IP-10 levels in cerebrospinal fluid are associated with neurotoxic tryptophan metabolites in acute central nervous system infectionsen_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright The Author(s) 2018
dc.source.journalJournal of Neuroinflammation

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