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

The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.

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
Open this paper in CoChat — free account

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…

Overview

Integrity signals

Registry

Crossref · 10.1016/j.cca.2005.06.013

Cites

0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Flagged first, then by citations

Show all 0 references

Research works printed but not linked: 71

  1. Yoshida, 1981, Induction of pulmonary indoleamine (2,3)-dioxygenase by interferon, Proc Natl Acad Sci U S A, 78, 129, 10.1073/pnas.78.1.129 · DOI
  2. Werner, 1987, Human macrophages degrade tryptophan upon induction by interferon gamma, Life Sci, 41, 273, 10.1016/0024-3205(87)90149-4 · DOI
  3. Hwu, 2000, Indoleamine 2,3-dioxygenase production by human dendritic cells results in the inhibition of T cell proliferation, J Immunol, 164, 3596, 10.4049/jimmunol.164.7.3596 · DOI
  4. Byrne, 1986, Induction of tryptophan degradation in vitro and in vivo: a gamma interferon stimulated activity, J Interferon Res, 6, 389, 10.1089/jir.1986.6.389 · DOI
  5. Werner-Felmayer, 1989, Characteristics of interferon induced tryptophan metabolism in human cells in vitro, Biochim Biophys Acta, 1012, 140, 10.1016/0167-4889(89)90087-6 · DOI
  6. Weiss, 1999, Modulation of neopterin formation and tryptophan degradation by Th1- and Th2-derived cytokines in human monocytic cells, Clin Exp Immunol, 116, 435, 10.1046/j.1365-2249.1999.00910.x · DOI
  7. Werner, 1988, Tryptophan degradation in patients infected by human immunodeficiency virus, Biol Chem Hoppe-Seyler, 369, 337, 10.1515/bchm3.1988.369.1.337 · DOI
  8. Fuchs, 1990, Decreased serum tryptophan in patients with HIV-1 infection correlates with increased serum neopterin and with neurologic/psychiatric symptoms, J Aquir Immune Defic Syndr, 3, 873
  9. Wirleitner, 2003, Immune activation and degradation of tryptophan in coronary heart disease, Eur J Clin Invest, 33, 550, 10.1046/j.1365-2362.2003.01186.x · DOI
  10. Denz, 1993, Weight loss in patients with hematological neoplasias is associated with immune system stimulation, Clin Investig, 71, 37, 10.1007/BF00210961 · DOI
  11. Heyes, 1992, Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurological disease, Brain, 115, 1249, 10.1093/brain/115.5.1249 · DOI
  12. Widner, 1997, Simultaneous measurement of serum tryptophan and kynurenine by HPLC, Clin Chem, 43, 2424, 10.1093/clinchem/43.12.2424 · DOI
  13. Wirleitner, 2003, Interferon-?-induced conversion of tryptophan: immunologic and neuropsychiatric aspects, Curr Med Chem, 10, 1581, 10.2174/0929867033457179 · DOI
  14. Pfefferkorn, 1984, Interferon gamma blocks the growth of Toxoplasma gondii in human fibroblasts by inducing the host cells to degrade tryptophan, Proc Natl Acad Sci U S A, 81, 908, 10.1073/pnas.81.3.908 · DOI
  15. de la Maza, 1988, Dependence of the in vitro antiproliferative activity of recombinant human gamma-interferon on the concentration of tryptophan in culture media, Cancer Res, 48, 346
  16. Ozaki, 1988, Induction of indoleamine 2,3-dioxygenase: a mechanism of the antitumor activity of interferon gamma, Proc Natl Acad Sci U S A, 85, 1242, 10.1073/pnas.85.4.1242 · DOI
  17. Munn, 1999, Inhibition of T cell proliferation by macrophage tryptophan catabolism, J Exp Med, 189, 1363, 10.1084/jem.189.9.1363 · DOI
  18. Munn, 2002, Potential regulatory function of human dendritic cells expressing indoleamine 2,3-dioxygenase, Science, 297, 1867, 10.1126/science.1073514 · DOI
  19. Grohmann, 2003, Tolerance, DCs and tryptophan: much ado about IDO, Trends Immunol, 24, 242, 10.1016/S1471-4906(03)00072-3 · DOI
  20. Terness, 2002, Inhibition of allogeneic T cell proliferation by indoleamine 2,3-dioxygenase-expressing dendritic cells: mediation of suppression by tryptophan metabolites, J Exp Med, 196, 447, 10.1084/jem.20020052 · DOI
  21. Frumento, 2002, Tryptophan-derived catabolites are responsible for inhibition of T and natural killer cell proliferation induced by indoleamine 2,3-dioxygenase, J Exp Med, 196, 459, 10.1084/jem.20020121 · DOI · Paper page
  22. Fuchs, 1989, Endogenous release of interferon-gamma and diminished response of peripheral blood mononuclear cells to antigenic stimulation, Immunol Lett, 23, 103, 10.1016/0165-2478(89)90120-X · DOI
  23. Laich, 2002, More rapid method for simultaneous measurement of tryptophan and kynurenine by HPLC, Clin Chem, 48, 579, 10.1093/clinchem/48.3.579 · DOI
  24. Steckel, 2005, Indoleamine 2,3-dioxygenase expression in monocytes of healthy nonpregnant women after induction with human choriongonadotropine, Scand J Immunol, 61, 213, 10.1111/j.0300-9475.2005.01538.x · DOI
  25. Widner, 2000, Interferon-gamma-induced tryptophan degradation: neuropsychiatry and immunological consequences, Curr Drug Metabol, 1, 193, 10.2174/1389200003339063 · DOI
  26. Fuchs, 1991, Increased endogenous interferon-gamma and neopterin correlate with increased degradation of tryptophan in human immunodeficiency virus type 1 infection, Immunol Lett, 28, 207, 10.1016/0165-2478(91)90005-U · DOI
  27. Huengsberg, 1998, Serum kynurenine-to-tryptophan ratio increases with progressive disease in HIV-infected patients, Clin Chem, 44, 858, 10.1093/clinchem/44.4.858 · DOI · Paper page
  28. Look, 2000, Parallel decrease in neurotoxin quinolinic acid and soluble tumor necrosis factor receptor p75 in serum during highly active antiretroviral therapy of HIV type 1 disease, AIDS Res Hum Retrovir, 16, 1215, 10.1089/08892220050116989 · DOI
  29. Gisslén, 1994, Tryptophan concentrations increase in cerebrospinal fluid and blood after zidovudine treatment in patients with HIV type 1 infection, AIDS Res Hum Retrovir, 10, 947, 10.1089/aid.1994.10.947 · DOI
  30. Zangerle, 2002, Effective antiretroviral therapy reduces degradation of tryptophan in patients with HIV-1 infection, Clin Immunol, 104, 242, 10.1006/clim.2002.5231 · DOI
  31. Pellegrin, 2005, Enhanced enzymatic degradation of tryptophan by indoleamine (2,3)-dioxygenase contributes to the tryptophan deficient state seen after major trauma, Shock, 23, 209
  32. Murr, 2001, Neopterin production and tryptophan degradation in humans infected by Streptococcus pyogenes, Med Microbiol Immunol, 189, 161, 10.1007/s430-001-8023-3 · DOI
  33. Fuchs, 1991, Kynurenine in cerebrospinal fluid of patients with Lyme neuroborreliosis, Immunol Infect Dis, 1, 271
  34. Wolf, 2004, Overexpression of indoleamine 2,3-dioxygenase (IDO) in human inflammatory bowel disease, Clin Immunol, 113, 47, 10.1016/j.clim.2004.05.004 · DOI
  35. Schroecksnadel, 2005, Tryptophan degradation in patients with gynecological cancer correlates with immune activation, Cancer Lett, 223, 323, 10.1016/j.canlet.2004.10.033 · DOI
  36. Iwagaki, 1995, Decreased serum tryptophan in patients with cancer cachexia correlates with increased serum neopterin, Immunol Invest, 24, 467, 10.3109/08820139509066843 · DOI
  37. Iwagaki, 1997, Cancer cachexia and depressive states: a neuro-endocrine-immunological disease?, Acta Med Okayama, 51, 233
  38. Giusti, 1996, Differential patterns of serum biomarkers of immune activation in human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic pararesis and adult T-cell leukemia/lymphoma, Cancer Epidemiol Biomark Prev, 5, 699
  39. Huang, 2002, Tryptophan decrease in advanced colorectal cancer correlates with immune activation and impaired quality of life, Br J Cancer, 86, 1691, 10.1038/sj.bjc.6600336 · DOI
  40. Widner, 2000, Enhanced tryptophan degradation in systemic lupus erythematosus, Immunobiology, 201, 621, 10.1016/S0171-2985(00)80079-0 · DOI
  41. Forrest, 2003, Kynurenine and neopterin levels in patients with rheumatoid arthritis and osteoporosis during drug treatment, Adv Exp Med Biol, 527, 287, 10.1007/978-1-4615-0135-0_32 · DOI
  42. Schroecksnadel, 2003, Increased degradation of tryptophan in blood of patients with rheumatoid arthritis, J Rheumatol, 30, 1935
  43. Widner, 2000, Tryptophan degradation and immune activation in Alzheimer's disease, J Neural Trans, 107, 343, 10.1007/s007020050029 · DOI
  44. Leblhuber, 1998, Activated immune system in patients with Huntington's disease, Clin Chem Lab Med, 36, 747, 10.1515/CCLM.1998.132 · DOI
  45. Widner, 2002, Increased neopterin production and tryptophan degradation in advanced Parkinson's disease, J Neural Trans, 109, 181, 10.1007/s007020200014 · DOI
  46. Frick, 2004, Increasing production of homocysteine and neopterin and degradation of tryptophan with older age, Clin Biochem, 37, 684, 10.1016/j.clinbiochem.2004.02.007 · DOI
  47. Brown, 1986, Effects of interferon and interleukin-2 on tryptophan metabolism in humans, J Cell Biochem Suppl, 10C, 230
  48. Wirleitner, 2002, Monocyte-derived dendritic cells release neopterin, J Leukoc Biol, 72, 1148, 10.1189/jlb.72.6.1148 · DOI
  49. Schroecksnadel, 1996, Decreased plasma tryptophan in pregnancy, Obstet Gynecol, 88, 47, 10.1016/0029-7844(96)00084-1 · DOI
  50. Schroecksnadel, 2003, Longitudinal study of tryptophan degradation during and after pregnancy, Life Sci, 72, 785, 10.1016/S0024-3205(02)02304-4 · DOI
  51. Munn, 1998, Prevention of allogeneic fetal rejection by tryptophan catabolism, Science, 281, 1191, 10.1126/science.281.5380.1191 · DOI
  52. Fuchs, 1989, Neopterin as a predictive marker for disease progression in human immunodeficiency virus type 1 infection, Clin Chem, 35, 1746, 10.1093/clinchem/35.8.1746 · DOI
  53. Fahey, 1990, The prognostic value of cellular and serologic markers in infection with human immunodeficiency virus type 1, N Engl J Med, 322, 166, 10.1056/NEJM199001183220305 · DOI
  54. Fuchs, 1990, Increased serum neopterin in patients with HIV-1 infection is correlated with reduced in vitro interleukin-2 production, Clin Exp Immunol, 80, 44, 10.1111/j.1365-2249.1990.tb06439.x · DOI
  55. Fuchs, 1991, Immune activation and the anaemia associated with chronic inflammatory disorders, Eur J Haematol, 46, 65, 10.1111/j.1600-0609.1991.tb00524.x · DOI
  56. Weiss, 2004, Possible role of cytokine-induced tryptophan degradation in anaemia of inflammation, Eur J Haematol, 72, 130, 10.1046/j.0902-4441.2003.00197.x · DOI
  57. Owens, 1994, Role of serotonin in the pathophysiology of depression: focus on the serotonin transporter, Clin Chem, 40, 288, 10.1093/clinchem/40.2.288 · DOI
  58. Murr, 2000, Immune reaction links disease progression in cancer patients with depression, Med Hypotheses, 55, 137, 10.1054/mehy.1999.1043 · DOI
  59. Widner, 2002, Neopterin production tryptophan degradation and mental depression: what is the link?, Brain Behav Immun, 16, 590, 10.1016/S0889-1591(02)00006-5 · DOI
  60. Launay, 1988, Decreased whole blood 5-hydroxytryptamine (serotonin) in AIDS patients, J Acquir Immune Defic Syndr, 1, 324
  61. Maes, 1994, Increased neopterin and interferon-gamma secretion and lower availability of l-tryptophan in major depression: further evidence for an immune response, Psych Res, 54, 143, 10.1016/0165-1781(94)90003-5 · DOI · Paper page
  62. DeVane, 1998, Differential pharmacology of newer antidepressants, J Clin Psych, 59, 85
  63. Suarez, 2001, Outcome of patients with HIV-1-related cognitive impairment on highly active antiretroviral therapy, AIDS, 15, 195, 10.1097/00002030-200101260-00008 · DOI
  64. Gendelman, 1998, Suppression of inflammatory neurotoxins by highly active antiretroviral therapy in human immunodeficiency virus-associated dementia, J Infect Dis, 178, 1000, 10.1086/515693 · DOI
  65. Judd, 2000, Depressive symptoms reduced in individuals with HIV/AIDS treated with highly active antiretroviral therapy: a longitudinal study, Aust NZ J Psychiatry, 34, 1015, 10.1080/000486700278 · DOI
  66. Murray, 2003, Tryptophan depletion and HIV infection: a metabolic link to pathogenesis, Lancet Infect Dis, 3, 644, 10.1016/S1473-3099(03)00773-4 · DOI
  67. Cady, 1991, 1-Methyl-dl-tryptophan, beta-(3-benzofuranyl)-dl-alanine (the oxygen analog of tryptophan), and beta-[3-benzo(b)thienyl]-dl-alanine (the sulfur analog of tryptophan) are competitive inhibitors for indoleamine 2,3-dioxygenase, Arch Biochem Biophys, 291, 326, 10.1016/0003-9861(91)90142-6 · DOI
  68. Winkler, 2004, St. John's wort (Hypericum perforatum) counteracts cytokine-induced tryptophan catabolism in vitro, Biol Chem, 385, 1197, 10.1515/BC.2004.155 · DOI
  69. Schroecksnadel, 2005, Aspirin down-regulates tryptophan degradation in stimulated human peripheral blood mononuclear cells in vitro, Clin Exp Immunol, 140, 41, 10.1111/j.1365-2249.2005.02746.x · DOI
  70. Winkler, 2004, In vitro effects of two extracts and two pure alkaloid preparations of Uncaria tomentosa on peripheral blood mononuclear cells, Planta Med, 70, 205, 10.1055/s-2004-815536 · DOI
  71. Murr, 2005, Antioxidants may increase the probability of developing allergic diseases and asthma, Med Hypotheses, 64, 973, 10.1016/j.mehy.2004.11.011 · DOI

Cited by

Sorted by citations

Items 501–503 of 503

Metadata

Authors
Schröcksnadel, K., Wirleitner, B., Winkler, C., & Fuchs, D.
Affiliations
Innsbruck Medical University (AT)
Corresponding author
Fuchs, Dietmar
ORCID
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review