The end of the road for the tryptophan depletion concept in pregnancy and infection
Author
Badawy, Abdulla
Namboodiri, Aryan
Moffett, John
Date
2016-06-29Acceptance date
2016-03-16
Type
Article
Publisher
Portland Press
ISSN
1470-8736
Metadata
Show full item recordAbstract
We hypothesize that: (1) L-tryptophan (Trp) is greatly utilized and not depleted in pregnancy; (2) fetal tolerance is achieved in part through immunosuppressive kynurenine (Kyn) metabolites produced by the flux of plasma free (non-albumin-bound) Trp down the Kyn pathway; (3) the role of indoleamine 2,3-dioxygenase (IDO) in infection is not related to limitation of an essential amino acid, but is rather associated with stress responses and the production of Kyn metabolites that regulate the activities of antigen presenting cells and T-cells, as well as increased NAD+ synthesis in IDO-expressing cells; (4) Trp depletion is not a host defence mechanism, but is a consequence of Trp utilization. We recommend that future studies in normal and abnormal pregnancies and in patients with infections or cancer should include measurements of plasma free Trp, determinants of Trp binding (albumin and non-esterified fatty acids), total Trp, determinants of activities of the Trp-degrading enzymes Trp 2,3-dioxygenase (TDO) (cortisol) and IDO (cytokines) and levels of Kyn metabolites. We also hypothesize that abnormal pregnancies and failure to combat infections or cancer may be associated with excessive Trp metabolism that can lead to pathological immunosuppression by excessive production of Kyn metabolites. Mounting evidence from many laboratories indicates that Trp metabolites are key regulators of immune cell behaviour, whereas Trp depletion is an indicator of extensive utilization of this key amino acid.
Journal/conference proceeding
Clinical Science;
Citation
Badawy, A.A.B., Namboodiri, A.M. and Moffett, J.R. (2016) 'The end of the road for the tryptophan depletion concept in pregnancy and infection', Clinical Science, 130(15), pp.1327-1333. DOI: 10.1042/CS20160153.
Description
Article published in Clinical Science on 29 June 2016, available open access at: https://doi.org/10.1042/CS20160153.
Closed deposit
Sponsorship
Cardiff Metropolitan University (Grant ID: Cardiff Metropolian (Internal))
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