A cross-sectional study of inflammatory markers as determinants of circulating kynurenines in the Lung Cancer Cohort Consortium

Øivind Midttun, Arve Ulvik, Klaus Meyer, Hana Zahed, Graham G. Giles, Jonas Manjer, Malte Sandsveden, Arnulf Langhammer, Elin Pettersen Sørgjerd, Annelie F. Behndig, Mikael Johansson, Neal D. Freedman, Wen Yi Huang, Chu Chen, Ross Prentice, Victoria L. Stevens, Ying Wang, Loïc Le Marchand, Stephanie J. Weinstein, Qiuyin CaiAlan A. Arslan, Yu Chen, Xiao Ou Shu, Wei Zheng, Jian Min Yuan, Woon Puay Koh, Kala Visvanathan, Howard D. Sesso, Xuehong Zhang, J. Michael Gaziano, Anouar Fanidi, Hilary A. Robbins, Paul Brennan, Mattias Johansson, Per M. Ueland

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

Sammanfattning

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.

Originalspråkengelska
Artikelnummer1011
TidskriftScientific Reports
Volym13
Nummer1
DOI
StatusPublished - 2023 dec.

Ämnesklassifikation (UKÄ)

  • Cancer och onkologi

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