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A cross-sectional study of inflammatory markers as determinants of circulating kynurenines in the Lung Cancer Cohort Consortium
Bevital AS, Laboratory Building, Bergen, Norway.
Bevital AS, Laboratory Building, Bergen, Norway.
Bevital AS, Laboratory Building, Bergen, Norway.
Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France.
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2023 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 13, no 1, article id 1011Article in journal (Refereed) Published
Abstract [en]

Circulating concentrations of metabolites (collectively called kynurenines) in the kynurenine pathway of tryptophan metabolism increase during inflammation, particularly in response to interferon-gamma (IFN-γ). Neopterin and the kynurenine/tryptophan ratio (KTR) are IFN-γ induced inflammatory markers, and together with C-reactive protein (CRP) and kynurenines they are associated with various diseases, but comprehensive data on the strength of associations of inflammatory markers with circulating concentrations of kynurenines are lacking. We measured circulating concentrations of neopterin, CRP, tryptophan and seven kynurenines in 5314 controls from 20 cohorts in the Lung Cancer Cohort Consortium (LC3). The associations of neopterin, KTR and CRP with kynurenines were investigated using regression models. In mixed models, one standard deviation (SD) higher KTR was associated with a 0.46 SD higher quinolinic acid (QA), and 0.31 SD higher 3-hydroxykynurenine (HK). One SD higher neopterin was associated with 0.48, 0.44, 0.36 and 0.28 SD higher KTR, QA, kynurenine and HK, respectively. KTR and neopterin respectively explained 24.1% and 16.7% of the variation in QA, and 11.4% and 7.5% of HK. CRP was only weakly associated with kynurenines in regression models. In summary, QA was the metabolite that was most strongly associated with the inflammatory markers. In general, the inflammatory markers were most strongly related to metabolites located along the tryptophan-NAD axis, which may support suggestions of increased production of NAD from tryptophan during inflammation.

Place, publisher, year, edition, pages
Springer Nature , 2023. Vol. 13, no 1, article id 1011
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Cancer and Oncology
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URN: urn:nbn:se:umu:diva-204156DOI: 10.1038/s41598-023-28135-9ISI: 001003289000030PubMedID: 36653422Scopus ID: 2-s2.0-85146485674OAI: oai:DiVA.org:umu-204156DiVA, id: diva2:1732074
Available from: 2023-01-30 Created: 2023-01-30 Last updated: 2023-09-05Bibliographically approved

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Behndig, Annelie F.Johansson, Mikael

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