Sternberg, J. M., Forrest, C. M., Dalton, R. N., Turner, C., Rodgers, J. , Stone, T. W. and Kennedy, P. G.E. (2017) Kynurenine pathway activation in Human African trypanosomiasis. Journal of Infectious Diseases, 215(5), pp. 806-812. (doi: 10.1093/infdis/jiw623) (PMID:28013248) (PMCID:PMC5388295)
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Abstract
Background: The kynurenine pathway of tryptophan oxidation is associated with CNS inflammatory pathways. Inhibition of this pathway ameliorates CNS inflammation in rodent models of the late (meningoencephalitic) stage of Human African trypanosomiasis (HAT). In this study we evaluate whether the kynurenine pathway is activated in clinical HAT and if it is associated with CNS inflammatory responses. Methods: We measured cerebrospinal fluid (CSF) tryptophan and kynurenine metabolite concentrations in Trypanosoma brucei rhodesiense patients using liquid chromatography-mass spectrometry. Results: Kynurenine concentration was increased in both early and late stage disease CSF, with a progressive increase in tryptophan oxidation associated with stage progression. Kynurenine pathway activation was associated with increases in neuroinflammatory markers but there was no clear relationship to neurological symptoms. Conclusions: CNS Kynurenine pathway activation occurs during HAT, including cases prior to the current diagnostic cut off for late stage infection, providing evidence for early CNS involvement in HAT. Metabolite data demonstrate that the kynurenine-3-monooxygenase and kynurenine aminotransferase branches of the kynurenine pathway are active. The association between tryptophan oxidation and CNS inflammatory responses as measured by CSF IL-6 concentration supports a role of kynurenine metabolites in the inflammatory pathogenesis of late stage HAT.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Forrest, Dr Caroline and Stone, Professor Trevor and Kennedy, Professor Peter and Rodgers, Dr Jean |
| Authors: | Sternberg, J. M., Forrest, C. M., Dalton, R. N., Turner, C., Rodgers, J., Stone, T. W., and Kennedy, P. G.E. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine |
| Journal Name: | Journal of Infectious Diseases |
| Publisher: | Oxford University Press |
| ISSN: | 0022-1899 |
| ISSN (Online): | 1537-6613 |
| Published Online: | 24 December 2016 |
| Copyright Holders: | Copyright © 2016 The Authors |
| First Published: | First published in Journal of Infectious Diseases 215(5):806-812 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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