A cross-sectional study of inflammatory markers as determinants of circulating kynurenines in the Lung Cancer Cohort Consortium
(2023) In Scientific Reports 13(1).- Abstract
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... (More)
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.
(Less)
- author
- organization
- publishing date
- 2023-12
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Scientific Reports
- volume
- 13
- issue
- 1
- article number
- 1011
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:36653422
- scopus:85146485674
- ISSN
- 2045-2322
- DOI
- 10.1038/s41598-023-28135-9
- language
- English
- LU publication?
- yes
- id
- 6718ed32-c402-4828-82c3-ecbb81892482
- date added to LUP
- 2024-01-12 12:22:20
- date last changed
- 2024-04-13 05:50:45
@article{6718ed32-c402-4828-82c3-ecbb81892482,
abstract = {{<p>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.</p>}},
author = {{Midttun, Øivind and Ulvik, Arve and Meyer, Klaus and Zahed, Hana and Giles, Graham G. and Manjer, Jonas and Sandsveden, Malte and Langhammer, Arnulf and Sørgjerd, Elin Pettersen and Behndig, Annelie F. and Johansson, Mikael and Freedman, Neal D. and Huang, Wen Yi and Chen, Chu and Prentice, Ross and Stevens, Victoria L. and Wang, Ying and Le Marchand, Loïc and Weinstein, Stephanie J. and Cai, Qiuyin and Arslan, Alan A. and Chen, Yu and Shu, Xiao Ou and Zheng, Wei and Yuan, Jian Min and Koh, Woon Puay and Visvanathan, Kala and Sesso, Howard D. and Zhang, Xuehong and Gaziano, J. Michael and Fanidi, Anouar and Robbins, Hilary A. and Brennan, Paul and Johansson, Mattias and Ueland, Per M.}},
issn = {{2045-2322}},
language = {{eng}},
number = {{1}},
publisher = {{Nature Publishing Group}},
series = {{Scientific Reports}},
title = {{A cross-sectional study of inflammatory markers as determinants of circulating kynurenines in the Lung Cancer Cohort Consortium}},
url = {{http://dx.doi.org/10.1038/s41598-023-28135-9}},
doi = {{10.1038/s41598-023-28135-9}},
volume = {{13}},
year = {{2023}},
}