Cited by 551Tryptophan and brain disordersAmino Acid Enzymes and MetabolismReproductive System and Pregnancy

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Monitoring tryptophan metabolism in chronic immune activation

Schröcksnadel, Katharina, Wirleitner, Barbara, Winkler, Christiana, Fuchs, Dietmar·2006·Clinica Chimica Acta

DOI 10.1016/j.cca.2005.06.013

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Abstract

The essential amino acid tryptophan is a constituent of proteins and is also a substrate for two important biosynthetic pathways: the generation of neurotransmitter 5-hydroxytryptamine (serotonin) by tryptophan 5-hydroxylase, and the formation of kynurenine derivatives and nicotinamide adenine dinucleotides. The latter pathway is initiated by the enzymes tryptophan pyrrolase (tryptophan 2,3-dioxygenase, TDO) and indoleamine 2,3-dioxygenase (IDO). TDO is located in liver cells, whereas IDO is expressed in a variety of cells including monocyte-derived macrophages and dendritic cells and is preferentially induced by Th1-type cytokine interferon-gamma. Tryptophan depletion via IDO is part of the cytostatic and antiproliferative activity mediated by interferon-gamma in cells. In vivo tryptophan concentration can be measured by HPLC by monitoring its natural fluorescence (285 nm excitation and 365 nm emission wavelength). IDO activity is characterized best by the kynurenine to tryptophan ratio which correlates with concentrations of immune activation markers such as neopterin. Low serum/plasma tryptophan concentration is observed in infectious, autoimmune, and malignant diseases and disorders that involve cellular (Th1-type) immune activation as well as during pregnancy due to accelerated tryptophan conversion. Thus, in states of persistent immune activation, low tryptophan concentration may contribute to immunodeficiency. Decreased serum tryptophan can also effect serotonin biosyn…

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“Tryptophan degradation by IDO was found to be necessary for induction of tolerance to the fetus [51].”
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Lian, Q., He, Z.-F., He, Q., Luo, A.-P., Yan, K., Zhang, D.-X., Lu, X.-Q., & Zhou, X.-B. (2014) · Analytica Chimica Acta · doi:10.1016/j.aca.2014.03.032 · Cited by 172
Characterization of Microbial Dysbiosis and Metabolomic Changes in Dogs with Acute Diarrhea
Guard, B. C., Barr, J. W., Reddivari, L., Klemashevich, C. L., Jayaraman, A., Steiner, J. M., Vanamala, J., & Suchodolski, J. S. (2015) · PLoS ONE · doi:10.1371/journal.pone.0127259 · Cited by 202
“patients and controls, one study found that serum tryptophan was decreased while the kynurenine/tryptophan ratio was increased in active CD [58].”
Background
Of mice, rats and men: Revisiting the quinolinic acid hypothesis of Huntington's disease
Schwarcz, R. M., Guidetti, P., Sathyasaikumar, K. V., & Muchowski, P. J. (2009) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2009.04.005 · Cited by 177
“…is currently primarily concerned with indoleamine-2,3-dioxygenase (IDO), one of the two enzymes responsible for the initial oxidative opening of tryptophan’s indole ring (the other one being the more substratespecific tryptophan-2,3-dioxygenase) (Schröcksnadel et al., 2006; Xu et al., 2008).”
Background
Associations of Plasma Kynurenines With Risk of Acute Myocardial Infarction in Patients With Stable Angina Pectoris
Pedersen, E. R., Tuseth, N., Eussen, S. J. P. M., Ueland, P. M., Strand, E., Svingen, G. F. T., Midttun, Ø., Meyer, K., Mellgren, G., Ulvik, A., et al. (2014) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.114.304674 · Cited by 171
“IFN-γ induces indoleamine 2,3-dioxygenase, which is the rate-limiting enzyme of the kynurenine (Kyn) pathway.(6) Through this route, the essential amino acid tryptophan (Trp) is metabolized into Kyn and several downstream metabolites, collectively referred to as kynurenines.”
Background
Neopterin, a prognostic marker in human malignancies
Sucher, R., Schroecksnadel, K., Weiß, G., Margreiter, R., Fuchs, D., & Brandacher, G. (2009) · Cancer Letters · doi:10.1016/j.canlet.2009.05.008 · Cited by 162
Self-citation
Plasma Biomarkers of Inflammation, the Kynurenine Pathway, and Risks of All-Cause, Cancer, and Cardiovascular Disease Mortality
Zuo, H., Ueland, P. M., Ulvik, A., Eussen, S. J. P. M., Vollset, S. E., Nygard, O. K., Midttun, Ø., Theofylaktopoulou, D., Meyer, K., & Tell, G. S. (2016) · American Journal of Epidemiology · doi:10.1093/aje/kwv242 · Cited by 169
“Positive associations of neopterin and KTR with mortality risk indicate a role of interferon-γ activity and T-helper 1type cellular immune activation (12).”
BackgroundInfluential
Tryptophan Metabolism and Related Pathways in Psychoneuroimmunology: The Impact of Nutrition and Lifestyle
Gostner, J. M., Geisler, S., Stonig, M., Mair, L., Sperner‐Unterweger, B., & Fuchs, D. (2019) · Neuropsychobiology · doi:10.1159/000496293 · Cited by 167
Self-citation
Serum Analysis of Tryptophan Catabolism Pathway: Correlation With Crohnʼs Disease Activity
Gupta, N., Thaker, A. I., Kanuri, N. D., Riehl, T. E., Rowley, C. W., Stenson, W. F., & Ciorba, M. A. (2011) · Inflammatory Bowel Diseases · doi:10.1002/ibd.21849 · Cited by 159
“bias generated by differences in dietary intake among individuals.(10,11,17,19) K/T ratios are shown at values 1000.”
Therapeutic Potential of Amino Acids in Inflammatory Bowel Disease
Liu, Y.-L., Wang, X.-Y., & Hu, C.-A. A. (2017) · Nutrients · doi:10.3390/nu9090920 · Cited by 143
The kynurenine pathway and inflammation in amyotrophic lateral sclerosis
Chen, Y., Stankovic, R., Cullen, K. M., Meininger, V., Garner, B., Coggan, S., Grant, R., Brew, B. J., & Guillemin, G. J. (2010) · Neurotoxicity Research · doi:10.1007/s12640-009-9129-7 · Cited by 141
“method used here is a modification of a published protocol (Schrocksnadel et al. 2006). CSF and serum samples were Neurotox Res (2010) 18:132–142 133”
Method
Systemic Markers of Interferon-γ–Mediated Immune Activation and Long-Term Prognosis in Patients With Stable Coronary Artery Disease
Pedersen, E. R., Midttun, Ø., Ueland, P. M., Schartum-Hansen, H., Seifert, R., Igland, J., Nordrehaug, J. E., Ebbing, M., Svingen, G. F. T., Bleie, Ø., et al. (2010) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.110.219329 · Cited by 139
Pathophysiology of atherothrombosis: Mechanisms of thrombus formation on disrupted atherosclerotic plaques
Asada, Y., Yamashita, A., Sato, Y. Z., & Hatakeyama, K. (2020) · Pathology International · doi:10.1111/pin.12921 · Cited by 162
Tryptophan degradation in irritable bowel syndrome: evidence of indoleamine 2,3-dioxygenase activation in a male cohort
Clarke, G. A., Fitzgerald, P., Cryan, J. F., Cassidy, E., Quigley, E. M. M., & Dinan, T. G. (2009) · BMC Gastroenterology · doi:10.1186/1471-230x-9-6 · Cited by 130
“Although there is considerable group overlap between tryptophan and kynurenine, the ratio is considered a more appropriate indicator of the degree of tryptophan degradation along this pathway than absolute measurement of its components [22].”
Age‐ and disease‐specific changes of the kynurenine pathway in Parkinson’s and Alzheimer’s disease
Sorgdrager, F. J. H., Vermeiren, Y., van Faassen, M. H. J. R., van der Ley, C., Nollen, E. A. A., Kema, I. P., & Deyn, P. P. D. (2019) · Journal of Neurochemistry · doi:10.1111/jnc.14843 · Cited by 158
“As inflammation is a key activator of the Kyn pathway (Schr€ocksnadel et al. 2006; Badawy 2017), the age-related Kyn pathway activation observed in our study could be related to changes in immune activation and functioning.”
Background
Immune Activation Driven by CTLA-4 Blockade Augments Viral Replication at Mucosal Sites in Simian Immunodeficiency Virus Infection
Cecchinato, V., Tryniszewska, E. A., Ma, Z. M., Vaccari, M., Boasso, A., Tsai, W.-P., Petrovas, C., Fuchs, D., Héraud, J., Venzon, D. J., et al. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.8.5439 · Cited by 127
“ICC staining was performed using the anti-TNF- , -IFN , and -IL-2 Abs.”
BackgroundInfluentialSelf-citation
The Immunopathogenesis of Alzheimer’s Disease Is Related to the Composition of Gut Microbiota
Leblhuber, F., Ehrlich, D., Steiner, K., Geisler, S., Fuchs, D., Lanser, L., & Kurz, K. (2021) · Nutrients · doi:10.3390/nu13020361 · Cited by 149
Self-citation
Inflammation in depression: is adiposity a cause?
Shelton, R. C., & Miller, A. H. (2011) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2011.13.1/rshelton · Cited by 143
“Activation of the enzyme idoleamine 2,3-dioxygenase— IDO (and the related liver enzyme tryptophan 2,3dioxygenase) is an alternative pathway for tryptophan metabolism yielding kynurenine (KYN) and leading to tryptophan depletion and ultimately decreased serotonin in brain.(32,33) Several cytokines and their signaling p…”
Fatigue in inflammatory rheumatic diseases: current knowledge and areas for future research
Davies, K., Dures, E. K., & Ng, W. (2021) · Nature Reviews Rheumatology · doi:10.1038/s41584-021-00692-1 · Cited by 147
Mining microbes for mental health: determining the role of microbial metabolic pathways in human brain health and disease
Spichak, S., Bastiaanssen, T. F. S., Berding, K., Vlckova, K., Clarke, G., Dinan, T. G., & Cryan, J. F. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.02.044 · Cited by 127
Tryptophan catabolism in females with irritable bowel syndrome: relationship to interferon‐gamma, severity of symptoms and psychiatric co‐morbidity
Fitzgerald, P., Eugene, M. C., Clarke, G. A., Scully, P., Barry, S., Eamonn, M. M. Q., Shanahan, F., Cryan, J. F., & Dinan, T. G. (2008) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2008.01195.x · Cited by 122
The skin as a mirror of the soul: exploring the possible roles of serotonin
Nordlind, K., Azmitia, E. C., & Slominski, A. T. (2007) · Experimental Dermatology · doi:10.1111/j.1600-0625.2007.00670.x · Cited by 132
A biological pathway linking inflammation and depression: activation of indoleamine 2,3-dioxygenase
Davies, Christmas, D. M., & Potokar, J. P. (2011) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s17573 · Cited by 121
“50”
Tryptophan hydroxylase-1 regulates immune tolerance and inflammation
Nowak, E. C., de Vries, V. C., Wasiuk, A., Ahonen, C. L., Bennett, K. A., Mercier, I. L., Ha, D.-G., & Noelle, R. J. (2012) · The Journal of Experimental Medicine · doi:10.1084/jem.20120408 · Cited by 129
“JEM Vol. 209, No. 11 Article 2129 levels of tryptophan are generally attributed to the activity of TDO, it appears that IDO can modulate the relative amounts of tryptophan under inflammatory conditions (Schröcksnadel et al., 2006).”
Background
CSF and plasma cytokines at delivery and postpartum mood disturbances
Boufidou, F., Lambrinoudaki, I., Argeitis, J., Zervas, I. M., Pliatsika, P., Leonardou, A. A., Petropoulos, G., Hassiakos, D., Papadias, K., & Nikolaou, C. (2008) · Journal of Affective Disorders · doi:10.1016/j.jad.2008.07.008 · Cited by 118
“Thus, the induction of IDO results in the decreased availability of serotonin and possibly depressive symptoms (Schrocksnadel et al., 2006).”
Background
Neopterin and kynurenine–tryptophan ratio as predictors of coronary events in older adults, the Hordaland Health Study
Sulo, G., Vollset, S. E., Nygard, O. K., Midttun, Ø., Ueland, P. M., Eussen, S. J. P. M., Pedersen, E. R., & Tell, G. S. (2013) · International Journal of Cardiology · doi:10.1016/j.ijcard.2012.12.090 · Cited by 120
“The KTR is considered amarker of cell mediated immune activation [11].”
Background
Serum Indoleamine 2,3-Dioxygenase Activity Predicts Prognosis of Pulmonary Tuberculosis
Suzuki, Y., Suda, T., Asada, K., Miwa, S., Suzuki, M., Fujie, M., Furuhashi, K., Nakamura, Y., Inui, N., Shirai, T., et al. (2012) · Clinical and Vaccine Immunology · doi:10.1128/cvi.05402-11 · Cited by 122
“IDO activity can be estimated using the Kyn-toTrp ratio, because Kyn is the first product formed through the catabolism of Trp, which is tightly regulated by IDO (11, 12, 14, 23).”
Method
Plasma tryptophan, kynurenine and 3-hydroxykynurenine measurement using automated on-line solid-phase extraction HPLC–tandem mass spectrometry
de Jong, W. H. A., Smit, R., Bakker, S. J. L., de Vries, E. G. E., & Kema, I. P. (2009) · Journal of Chromatography B · doi:10.1016/j.jchromb.2009.01.015 · Cited by 109
Tryptophan Metabolism in Patients With Chronic Kidney Disease Secondary to Type 2 Diabetes: Relationship to Inflammatory Markers
Debnath, S., Velagapudi, C., Redus, L., Thameem, F., Kasinath, B. S., Hura, C., Lorenzo, C., Abboud, H. E., & O’Connor, J. C. (2017) · International Journal of Tryptophan Research · doi:10.1177/1178646917694600 · Cited by 132
Disturbed Tryptophan Metabolism in Cardiovascular Disease
Mangge, H., Stelzer, I., Reininghaus, E. Z., Weghuber, D., Postolache, T. T., & Fuchs, D. (2014) · Current Medicinal Chemistry · doi:10.2174/0929867321666140304105526 · Cited by 133
“Thus, increased TRP catabolism was proposed as a pathway leading to mood dysregulation [1].”
BackgroundSelf-citation
Indoleamine 2,3 dioxygenase in intestinal disease
Ciorba, M. A. (2012) · Current Opinion in Gastroenterology · doi:10.1097/mog.0b013e32835c9cb3 · Cited by 117
“Using this ratio (versus either alone) limits the potential bias related to differences in the dietary intake of tryptophan [37].”
Background
Immunomodulation mechanism of antidepressants: interactions between serotonin/norepinephrine balance and Th1/Th2 balance
Martino, M., Rocchi, G., Escelsior, A., & Fornaro, M. (2012) · Current Neuropharmacology · doi:10.2174/157015912800604542 · Cited by 111
“Therefore, in course of chronic immune activation, decreased serum tryptophan, associated with 5-HT reduced synthesis [225, 226] and hypercortisolism [226], was found parallel to the course of malignant diseases [227].”
Background
Regulatory T-Cell Markers, Indoleamine 2,3-Dioxygenase, and Virus Levels in Spleen and Gut during Progressive Simian Immunodeficiency Virus Infection
Boasso, A., Vaccari, M., Hryniewicz, A., Fuchs, D., Nacsa, J., Cecchinato, V., Andersson, J., Franchini, G., Shearer, G. M., & Chougnet, C. A. (2007) · Journal of Virology · doi:10.1128/jvi.00760-07 · Cited by 106
“Because non-IDO-mediated Trp degradation can also occur at hepatic level, we measured plasma concentration of neopterin, which is a reliable marker for cytokine-induced IDO-mediated Trp catabolism (38).”
BackgroundSelf-citation
Prenatal depression and anxiety in Toxoplasma gondii positive women
Groer, M., Yolken, R., Xiao, J., Beckstead, J., Fuchs, D., Mohapatra, S., Seyfang, A., & Postolache, T. (2011) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2011.01.004 · Cited by 106
“(IDO), which metabolizes tryptophan to kynurenine and depletes serotonin.(6,7)”
Self-citation
Metabolic phenotyping reveals a reduction in the bioavailability of serotonin and kynurenine pathway metabolites in both the urine and serum of individuals living with Alzheimer’s disease
Whiley, L., Chappell, K. E., D’Hondt, E., Lewis, M. R., Jiménez, B., Snowden, S. G., Soininen, H. S., Kłoszewska, I., Mecocci, P., Tsolaki, M., et al. (2021) · Alzheimer s Research & Therapy · doi:10.1186/s13195-020-00741-z · Cited by 126
“The activity of IDO can be monitored using the circulating kynurenine/tryptophan ratio [16].”
BackgroundMethod
Untargeted metabolomics of COVID-19 patient serum reveals potential prognostic markers of both severity and outcome
Roberts, I., Muelas, M. W., Taylor, J. M., Davison, A., Yun Xu, A., Grixti, J. M., Gotts, N., Sorokin, A., Goodacre, R., & Kell, D. B. (2021) · Metabolomics · doi:10.1007/s11306-021-01859-3 · Cited by 113
“The degradation of tryptophan to kynurenine is often associated with increase in inflammatory processes (Schröcksnadel et al., 2006).”
Background
PRE- AND POSTNATAL EXPOSURE TO KYNURENINE CAUSES COGNITIVE DEFICITS IN ADULTHOOD
Pocivavsek, A., Wu, H., Elmer, G. I., Bruno, J. P., & Schwarcz, R. (2012) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2012.08064.x · Cited by 105
“In the blood, IDO stimulation leads to an increase in the formation of l-kynurenine (‘kynurenine’; Schröcksnadel et al., 2006), a pivotal kynurenine pathway metabolite, which is readily transported”
M. tuberculosis Induces Potent Activation of IDO-1, but This Is Not Essential for the Immunological Control of Infection
Blumenthal, A., Nagalingam, G., Huch, J. H., Walker, L., Guillemin, G. J., Smythe, G. A., Ehrt, S., Britton, W. J., & Saunders, B. M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0037314 · Cited by 105
“IDO-2 remained unchanged during Plasmodium berghei ANKA infection [46] and TDO activity has also not been associated with immunerelated tryptophan metabolism [47].”
Background
Th17/Treg Imbalance in Murine Cystic Fibrosis Is Linked to Indoleamine 2,3-Dioxygenase Deficiency but Corrected by Kynurenines
Iannitti, R. G., Carvalho, A., Cunha, C., LUCA, A. D., Giovannini, G., Casagrande, A., Zelante, T., Vacca, C., Fallarino, F., Puccetti, P., et al. (2013) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201207-1346oc · Cited by 107
“The kynurenine-to-tryptophan ratio was determined as described (28).”
BackgroundMethod
Effects of Exhaustive Aerobic Exercise on Tryptophan-Kynurenine Metabolism in Trained Athletes
Strasser, B., Geiger, D., Schauer, M., Gatterer, H., Burtscher, M., & Fuchs, D. (2016) · PLoS ONE · doi:10.1371/journal.pone.0153617 · Cited by 101
Self-citation
Quantitative profiling of folate and one-carbon metabolism in large-scale epidemiological studies by mass spectrometry
Ueland, P. M., Midttun, Ø., Windelberg, A., Svardal, A. M., Skålevik, R., & Hustad, S. (2007) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2007.339 · Cited by 94
Kynurenine pathway metabolism and immune activation: Peripheral measurements in psychiatric and co-morbid conditions
Strasser, B., Becker, K., Fuchs, D., & Gostner, J. M. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.02.030 · Cited by 97
“A decrease of tryptophan levels and an increase kynurenine to tryptophan ratio (Kyn/Trp) was found in several pathologies that are associated with chronic immune activation (Schroecksnadel et al., 2006), and this decrease was ascribed to inflammation-induced IDO-1 activity.”
InfluentialSelf-citation
Kynurenine pathway in psychosis: evidence of increased tryptophan degradation
Barry, S., Clarke, G., Scully, P., & Dinan, T. (2009) · Journal of Psychopharmacology · doi:10.1177/0269881108089583 · Cited by 96
Food preservatives sodium benzoate and propionic acid and colorant curcumin suppress Th1-type immune response in vitro
Maier, E., Kurz, K., Jenny, M., Schennach, H., Ueberall, F., & Fuchs, D. (2010) · Food and Chemical Toxicology · doi:10.1016/j.fct.2010.04.042 · Cited by 90
Self-citation
Enzymology of mammalian NAD metabolism in health and disease
Magni, G. (2008) · Frontiers in bioscience · doi:10.2741/3143 · Cited by 93
Natural Molecules and Neuroprotection: Kynurenic Acid, Pantethine and α-Lipoic Acid
Tóth, F., Cseh, E. K., & Vécsei, L. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22010403 · Cited by 105
“dioxygenase (IDO) [35] and tryptophan 2,3-dioxygenase (TDO) enzymes [36], the rate-”
Background
Pain/Depression Dyad: A Key to a Better Understanding and Treatment of Functional Somatic Syndromes
Goldenberg, D. L. (2010) · The American Journal of Medicine · doi:10.1016/j.amjmed.2010.01.014 · Cited by 94
Metabolomics Study of Immune Responses of New Zealand Greenshell™ Mussels (Perna canaliculus) Infected with Pathogenic Vibrio sp.
Nguyen, T. V., Alfaro, A. C., Young, T., Ravi, S., & Mérien, F. (2018) · Marine Biotechnology · doi:10.1007/s10126-018-9804-x · Cited by 102
“It is also a substrate for other major biosynthetic routes, such as the synthesis of serotonin, essent ial cel lular factors and the kynurenine pathway (Schröcksnadel et al. 2006).”
Background
A tryptophan metabolite, kynurenine, promotes mast cell activation through aryl hydrocarbon receptor
Kawasaki, H., Chang, H. ‐., Tseng, H.-C., Hsu, S., Yang, S. ‐., Hung, C. ‐., Zhou, Y., & Huang, S. (2014) · Allergy · doi:10.1111/all.12346 · Cited by 91
“This latter pathway is initiated by cleavage of the indole ring by two different rate-limiting enzymes: indoleamine 2,3-dioxygenase (IDO) found in many immune cells, such as dendritic cells and macrophages, and tryptophan 2,3-dioxygenase (TDO) located in not only liver and neuron, but also some tumor cells such as mal…”
Background
Mycobacterium Leprae –Host-Cell Interactions and Genetic Determinants in Leprosy: an Overview
Pinheiro, R. O., Sales, J. D. S., Sarno, E. N., & Sampaio, E. P. (2011) · Future Microbiology · doi:10.2217/fmb.10.173 · Cited by 83
Serum tryptophan, kynurenine, phenylalanine, tyrosine and neopterin concentrations in 100 healthy blood donors
Geisler, S., Mayersbach, P., Becker, K., Schennach, H., Fuchs, D., & Gostner, J. M. (2015) · Pteridines · doi:10.1515/pterid-2014-0015 · Cited by 91
“IDO converts the essential amino acid L-tryptophan (TRP) to kynurenine (KYN), which is the first and rate-limiting step of tryptophan catabolism.”
BackgroundInfluentialSelf-citation
In vitro testing for anti-inflammatory properties of compounds employing peripheral blood mononuclear cells freshly isolated from healthy donors
Jenny, M., Klieber, M., Zaknun, D., Schroecksnadel, S., Kurz, K., Ledochowski, M., Schennach, H., & Fuchs, D. (2010) · Inflammation Research · doi:10.1007/s00011-010-0244-y · Cited by 73
“comparing kyn and kyn/trp in serum or plasma, kyn/trp is certainly superior because of greater variance of trp concentrations in humans [ 16 ].”
BackgroundSelf-citation
Low Plasma Vitamin B-6 Status Affects Metabolism through the Kynurenine Pathway in Cardiovascular Patients with Systemic Inflammation1–4
Midttun, Ø., Ulvik, A., Pedersen, E. R., Ebbing, M., Bleie, Ø., Schartum-Hansen, H., Nilsen, R. M., Nygard, O. K., & Ueland, P. M. (2011) · Journal of Nutrition · doi:10.3945/jn.110.133082 · Cited by 80
Overproduction of Gastrointestinal 5-HT Promotes Colitis-Associated Colorectal Cancer Progression via Enhancing NLRP3 Inflammasome Activation
Li, T., Fu, B., Zhang, X., Zhou, Y., Yang, M., Cao, M., Chen, Y., Tan, Y., & Hu, R. (2021) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-20-1043 · Cited by 113
Inflammation‐induced activation of the indoleamine 2,3‐dioxygenase pathway: Relevance to cancer‐related fatigue
Kim, S., Miller, B. J., Stefanek, M. E., & Miller, A. H. (2015) · Cancer · doi:10.1002/cncr.29302 · Cited by 93
“expressed in the liver in response to TRP, KYN, and glucocorticoids and regulates systemic TRP levels.(28) On the other hand, IDO can be found in various cells throughout”
Background
Visceral Inflammation and Immune Activation Stress the Brain
Holzer, P., Farzi, A., Hassan, A. M., Zenz, G., Jačan, A., & Reichmann, F. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01613 · Cited by 84
“These behavioral perturbations are associated with disruption of the BBB, enhanced expression of indoleamine 2,3-dioxygenase (IDO) in hippocampus and 10 Holzer et al. Immune Activation Stresses the Brain Frontiers in Immunology | www.frontiersin.org November 2017 | Volume 8 | Article 1613 frontal cortex, suppression o…”
BackgroundInfluential
Chromatographic analysis of tryptophan metabolites
Sadok, I., Gamian, A., & Staniszewska, M. M. (2017) · Journal of Separation Science · doi:10.1002/jssc.201700184 · Cited by 102
“The neurodegenerative disorders affecting older people can be explained by the observation that [Kyn]/[Trp] ratio correlates with the level of neopterin, an immune activation marker [53] the concentration of which in the central nervous system increases with age in women [54].”
Background
Tryptophan Metabolism in Allergic Disorders
Gostner, J. M., Becker, K., Kofler, H., Strasser, B., & Fuchs, D. (2016) · International Archives of Allergy and Immunology · doi:10.1159/000445500 · Cited by 92
Self-citation
Urinary excretion of kynurenine and tryptophan, cardiovascular events, and mortality after elective coronary angiography.
Pedersen, E., Svingen, G., Schartum-Hansen, H., Ueland, P., Ebbing, M., Nordrehaug, J., Igland, J., Seifert, R., Nilsen, R. M., & Nygård, O. (2013) · European Heart Journal · doi:10.1093/eurheartj/eht264 · Cited by 84
“Since IDO is not expressed unless stimulated by IFN-g,(5) increased degradation of tryptophan is typically seen in states of activated cellular (Th1) immune responses.(6) Lowered endogenous tryptophan and kynurenine levels, however, occur when dietary intake of tryptophan is restricted.”
BackgroundInfluential
The role of indoleamine 2,3-dioxygenase in transplantation
Hainz, U., Jürgens, B., & Heitger, A. (2006) · Transplant International · doi:10.1111/j.1432-2277.2006.00370.x · Cited by 59
“In general, enhanced tryptophan degradation is observed in conditions of sustained cellular immune activation [26,44].”
Background
Accumulation of an Endogenous Tryptophan-Derived Metabolite in Colorectal and Breast Cancers
Puccetti, P., Fallarino, F., Italiano, A., Soubeyran, I., MacGrogan, G. M., Debled, M., Velasco, V., Bodet, D., Eimer, S., Veldhoen, M., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0122046 · Cited by 87
The Kynurenine Pathway: A Primary Resistance Mechanism in Patients with Glioblastoma
Sordillo, P. P., Sordillo, L. A., & Helson, L. (2017) · Anticancer Research · doi:10.21873/anticanres.11551 · Cited by 73
Indoleamine 2,3-dioxygenase regulates anti-tumor immunity in lung cancer by metabolic reprogramming of immune cells in the tumor microenvironment
Schafer, C. C., Wang, Y., Hough, K. P., Sawant, A., Grant, S. C., Thannickal, V. J., Zmijewski, J. W., Ponnazhagan, S., & Deshane, J. S. (2016) · Oncotarget · doi:10.18632/oncotarget.12249 · Cited by 84
“Increased IDO expression and activity are correlated with poor patient prognosis and quality of life [4, 5].”
Background
Knock-on effect of periodontitis to the pathogenesis of Alzheimer’s disease?
Leblhuber, F., Huemer, J., Steiner, K., Gostner, J. M., & Fuchs, D. (2020) · Wiener klinische Wochenschrift · doi:10.1007/s00508-020-01638-5 · Cited by 77
Self-citation
Imaging Correlates of Differential Expression of Indoleamine 2,3-Dioxygenase in Human Brain Tumors
Batista, C. E. A., Juhász, C., Muzik, O., Kupsky, W. J., Barger, G. R., Chugani, H. T., Mittal, S., Sood, S., Chakraborty, P. K., & Chugani, D. C. (2009) · Molecular Imaging and Biology · doi:10.1007/s11307-009-0225-0 · Cited by 75
“In mammals, most of the tryptophan derived from the diet is converted via the kynurenine pathway [36], which is upregulated in several autoimmune disorders and malignant neoplasms [35].”
Amino Acids and Their Metabolism in Atherosclerosis
Nitz, K., Lacy, M., & Atzler, D. (2019) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.118.311572 · Cited by 95
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“an indirect measure of IDO activity (11, 13).”
Background

Authors: Schröcksnadel, K., Wirleitner, B., Winkler, C., & Fuchs, D.
Affiliations: Innsbruck Medical University (AT)
Corresponding author: Fuchs, Dietmar
ORCID: Wirleitner, Barbara
Fuchs, Dietmar
Venue: Clinica Chimica Acta
Publisher: Elsevier BV
Published: 2006-02
Volume: 364
Issue: 1-2
Pages: 82-90
ISSN: 0009-8981 (ISSN-L)
DOI: 10.1016/j.cca.2005.06.013
OpenAlex: W2042985653
Cited by: 551
References: 0
Citations by year: 2026: 7 · 2025: 25 · 2024: 19 · 2023: 24 · 2022: 32 · 2021: 47 · 2020: 31 · 2019: 21 · 2018: 27 · 2017: 34 · 2016: 26 · 2015: 32 · 2014: 24 · 2013: 38 · 2012: 36
FWCI: 0.80
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Clinica Chimica Acta (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
Keywords: tryptophan metabolism, tryptophan depletion, indoleamine 2,3-dioxygenase, tryptophan 2,3-dioxygenase, kynurenine pathway, serotonin synthesis, interferon-gamma, chronic immune activation, Th1 response, neopterin, immunodeficiency, anemia, mood disorders, autoimmune disease, infectious diseases, pregnancy
MeSH terms: Autoimmune Diseases, Humans, Infections, Kynurenine, Neoplasms, Serotonin, Tryptophan, Tryptophan Hydroxylase, Tryptophan Oxygenase, Indoleamine-Pyrrole 2,3,-Dioxygenase

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Monitoring tryptophan metabolism in chronic immune activation

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