Diminished quality of life in patients with cancer correlates with tryptophan degradation

  • Katharina Schroecksnadel
  • Michael Fiegl
  • Karin Prassl
  • Christiana Winkler
  • Hubert A. Denz
  • Dietmar Fuchs
Original Paper



Quality of life (QoL) is frequently impaired in patients suffering from malignant disease. Disturbed metabolism of neurotransmitter serotonin might be crucially involved, and serotonin-precursor tryptophan is degraded during pro-inflammatory immune response. In this study, we compared QoL and fatigue self-rating scores of patients with various types of malignancy with tryptophan metabolic changes and immune activation status.


Venous blood was collected from 146 patients with gastrointestinal tumors (n = 43), hematological malignancy (n = 40), gynecological neoplasms (n = 26), lung cancer (n = 20) and from tumors of other localization (n = 17).


QoL was significantly reduced in patients suffering from progressive tumor disease in comparison to stable or remitting disease, also feeling of fatigue was increased (both P < 0.001). Serum tryptophan concentrations were lower in patients with progressive disease (P < 0.01), and decreased tryptophan concentrations were related to decreased QoL (r s = 0.256, P < 0.01) and increased fatigue (r s = −0.179; P < 0.05). Concentrations of tryptophan and kynurenine and the kynurenine to tryptophan ratio were predictive for impaired QoL and increased fatigue in univariate regression analysis, in multivariate analysis higher ESR and neopterin concentration in combination with stage of disease predicted QoL deterioration.


Results suggest that immune-mediated tryptophan degradation may contribute to cancer-induced QoL deterioration.


Tryptophan degradation Cancer Quality of life Neopterin Immune activation Fatigue 



This work was supported by the “Stiftung Propter Homines, Vaduz -Fürstentum Liechtenstein”, by the government of the State of the Austrian Tyrol, and by the European Community, Project #019031 BAMOD “Austrian Cancer Society/Tyrol”. We thank Miss Astrid Haara for excellent technical assistance.


  1. Allen-Mersh TG, Glover C, Fordy C, Henderson DC, Davies M (1998) Relation between depression and circulating immune products in patients with advanced colorectal cancer. J R Soc Med 91:408–413PubMedGoogle Scholar
  2. Bower J E, Ganz P A, Aziz N, Fahey JL (2002) Fatigue and proinflammatory cytokine activity in breast cancer survivors. Psychosom Med 64:604–611PubMedGoogle Scholar
  3. Brown RR, Ozaki Y, Datta S P, Borden EC, Sondel PM, Malone DG (1991) Implications of interferon-induced tryptophan catabolism in cancer auto-immune diseases and AIDS. Adv Exp Med Biol 294:425–435PubMedGoogle Scholar
  4. Capuron L, Ravaud A, Gualde N, Bosmans E, Dantzer R, Maes M, Neveu PJ (2001) Association between immune activation and early depressive symptoms in cancer patients treated with interleukin-2-based therapy. Psychoneuroendocrinology 26:797–808PubMedCrossRefGoogle Scholar
  5. Capuron L, Neurauter G, Musselman DL, Lawson DH, Nemeroff CB, Fuchs D, Miller AH (2003) Interferon-alpha-induced changes in tryptophan metabolism relationship to depression and paroxetine treatment. Biol Psychiatry 54:906–914PubMedCrossRefGoogle Scholar
  6. Carlin JM, Ozaki Y, Byrne GI, Brown RR, Borden EC (1989) Interferons and indoleamine 2 3-dioxygenase: role in antimicrobial and antitumor effects. Experientia 45:535–541PubMedCrossRefGoogle Scholar
  7. Cleeland CS, Bennett GJ, Dantzer R, Dougherty PM, Dunn AJ, Meyers CA, Miller AH, Payne R, Reuben JM, Wang XS, Lee BN (2003) Are the symptoms of cancer and cancer treatment due to a shared biologic mechanism? A cytokine-immunologic model of cancer symptoms. Cancer 97:2919–2925PubMedCrossRefGoogle Scholar
  8. Cruess DG, Petitto JM, Leserman J, Douglas SD, Gettes DR, Ten Have TR, Evans DL. (2003) Depression and HIV infection: impact on immune function and disease progression. CNS Spectr 8:52–58PubMedGoogle Scholar
  9. Dantzer R, Bluthe RM, Gheusi G, Cremona S, Laye S, Parnet P, Kelley KW (1998) Molecular basis of sickness behaviour. Ann NY Acad Sci 856:132–138PubMedCrossRefGoogle Scholar
  10. Denz H, Fuchs D, Huber H, Nachbaur D, Reibnegger G, Thaler J, Werner ER, Wachter H (1990) Correlation between neopterin interferon-gamma and haemoglobin in patients with haematological disorders. Eur J Haematol 44:186–189PubMedCrossRefGoogle Scholar
  11. Denz H, Orth B, Weiss G, Herrmann R, Huber P, Wachter H, Fuchs D (1993) Weight loss in patients with hematological neoplasias is associated with immune system stimulation. Clin Investig 71:37–41PubMedCrossRefGoogle Scholar
  12. Dimeo F, Schmittel A, Fietz T, Schwartz S, Kohler P, Boning D, Thiel E (2004) Physical performance depression immune status and fatigue in patients with hematological malignancies after treatment. Ann Oncol 15:1237–1242PubMedCrossRefGoogle Scholar
  13. Earlam S, Glover C, Fordy C, Burke D, Allen-Mersh TG (1996) Relation between tumor size quality of life and survival in patients with colorectal liver metastases. J Clin Oncol 14:171–175PubMedGoogle Scholar
  14. Fuchs D, Moeller AA, Reibnegger G, Werner ER, Werner-Felmayer G, Dierich MP, Wachter H (1991) Increased endogenous interferon-gamma and neopterin correlate with increased degradation of tryptophan in human immunodeficiency virus type 1 infection. Immunol Lett 28:207–211PubMedCrossRefGoogle Scholar
  15. Giusti RM, Maloney EM, Hanchard B, Morgan OS, Steinberg SM, Wachter H, Williams E, Cranston B, Fuchs D, Manns A (1996) Differential patterns of serum biomarkers of immune activation in human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis and adult T-cell leukemia/lymphoma. Cancer Epidemiol Biomarkers Prev 5:699–704PubMedGoogle Scholar
  16. Huang A, Fuchs D, Widner B, Glover C, Henderson DC, Allen-Mersh TG (2002) Serum tryptophan decrease correlates with immune activation and impaired quality of life in colorectal cancer. Br J Cancer 86:1691–1696PubMedCrossRefGoogle Scholar
  17. Iwagaki H, Hizuta A, Tanaka N, Orita K (1995) Decreased serum tryptophan in patients with cancer cachexia correlates with increased serum neopterin. Immunol Invest 24:467–478PubMedGoogle Scholar
  18. Iwagaki H, Hizuta A, Uomoto M, Takeuchi Y, Saito S, Tanaka N (1997) Cancer cachexia and depressive states: a neuro-endocrine-immunological disease? Acta Med Okayama 51:233–236PubMedGoogle Scholar
  19. Kronberger P, Weiss G, Tschmelitsch J, Fuchs D, Salzer GM, Wachter H, Reibnegger G (1995) Predictive value of urinary neopterin in patients with lung cancer. Eur J Clin Chem Clin Biochem 33:831–837PubMedGoogle Scholar
  20. Kurzrock R (2001) The role of cytokines in cancer-related fatigue. Cancer 92:1684–1688PubMedCrossRefGoogle Scholar
  21. Lewenhaupt A, Ekman P, Eneroth P, Eriksson A, Nilsson B, Nordstrom L (1986) Serum levels of neopterin as related to the prognosis of human prostatic carcinoma. Eur Urol 12:422–425PubMedGoogle Scholar
  22. Mahmoud FA, Rivera NI (2002) The role of C-reactive protein as a prognostic indicator in advanced cancer. Curr Oncol Rep 4:250–255PubMedGoogle Scholar
  23. Murr C, Bergant A, Widschwendter M, Heim K, Schrocksnadel H, Fuchs D (1999) Neopterin is an independent prognostic variable in females with breast cancer. Clin Chem 45:1998–2004PubMedGoogle Scholar
  24. Murr C, Widner B, Sperner-Unterweger B, Ledochowski M, Schubert C, Fuchs D (2000) Immune reaction links disease progression in cancer patients with depression. Med Hypotheses 55:137–140PubMedCrossRefGoogle Scholar
  25. Myint AM, Kim YK (2003) Cytokine-serotonin interaction through IDO: a neurodegeneration hypothesis of depression. Med Hypotheses 61:519–525PubMedCrossRefGoogle Scholar
  26. Platten M, Ho PP, Youssef S, Fontoura P, Garren H, Hur EM, Gupta R, Lee LY, Kidd BA, Robinson WH, Sobel RA, Selley ML, Steinman L (2005) Treatment of autoimmune neuroinflammation with a synthetic tryptophan metabolite. Science 310:850–855PubMedCrossRefGoogle Scholar
  27. Reibnegger G J, Bichler A H, Dapunt O, Fuchs DN, Fuith LC, Hausen A, Hetzel HM, Lutz H, Werner ER, Wachter H (1986) Neopterin as a prognostic indicator in patients with carcinoma of the uterine cervix. Cancer Res 46:950–955PubMedGoogle Scholar
  28. Reibnegger G, Hetzel H, Fuchs D, Fuith LC, Hausen A, Werner ER, Wachter H (1987) Clinical significance of neopterin for prognosis and follow-up in ovarian cancer. Cancer Res 47:4977–4981PubMedGoogle Scholar
  29. Schroecksnadel K, Winkler C, Fuith L C, Fuchs D (2005) Tryptophan degradation in patients with gynecological cancer correlates with immune activation. Cancer Lett 223:323–299PubMedCrossRefGoogle Scholar
  30. Taylor MW, Feng GS (1991) Relationship between interferon-gamma indoleamine 2 3-dioxygenase and tryptophan catabolism. FASEB J 5:2516–2522PubMedGoogle Scholar
  31. UICC (1997) TNM-Klassifikation maligner Tumoren 5th edition Wittekind CH, Wagner G (eds) Springer, Berlin Google Scholar
  32. Uyttenhove C, Pilotte L, Theate I, Stroobant V, Colau D, Parmentier N, Boon T, Van den Eynde BJ (2003) Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med 9:1269–1274PubMedCrossRefGoogle Scholar
  33. Weiss G, Kronberger P, Conrad F, Bodner E, Wachter H, Reibnegger G (1993) Neopterin and prognosis in patients with adenocarcinoma of the colon. Cancer Res 53:260–265PubMedGoogle Scholar
  34. Werner E R, Werner-Felmayer G, Fuchs D, Hausen A, Reibnegger G, Wachter H (1989) Parallel induction of tetrahydrobiopterin biosynthesis and indoleamine 2 3-dioxygenase activity in human cells and cell lines by interferon-gamma. Biochem J 262:861–866PubMedGoogle Scholar
  35. Widner B, Werner ER, Schennach H, Wachter H, Fuchs D (1997) Simultaneous measurement of serum tryptophan and kynurenine by HPLC. Clin Chem 43:2424–2426PubMedGoogle Scholar
  36. Widner B, Sepp N, Kowald E, Ortner U, Wirleitner B, Fritsch P, Baier-Bitterlich G, Fuchs D (2000) Enhanced tryptophan degradation in systemic lupus erythematosus. Immunobiology 201:621–630PubMedGoogle Scholar
  37. Widner B, Laich A, Sperner-Unterweger B, Ledochowski M, Fuchs D (2002) Neopterin production tryptophan degradation and mental depression—what is the link? Brain Behav Immun 16:590–595PubMedCrossRefGoogle Scholar
  38. Wirleitner B, Neurauter G, Schrocksnadel K, Frick B, Fuchs D (2003) Interferon-gamma-induced conversion of tryptophan: immunologic and neuropsychiatric aspects. Curr Med Chem 10:1581–1591PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Katharina Schroecksnadel
    • 1
  • Michael Fiegl
    • 2
  • Karin Prassl
    • 2
  • Christiana Winkler
    • 1
  • Hubert A. Denz
    • 2
  • Dietmar Fuchs
    • 1
  1. 1.Division of Biological Chemistry, BiocenterInnsbruck Medical UniversityInnsbruckAustria
  2. 2.Division of OncologyHospital Natters/InnsbruckNattersAustria

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