Abstract
Systemic lupus erythematosus (SLE), a progressive autoimmune disorder, is associated with chronic stimulation of various components of the immune system. Since cell-mediated immunity is also activated, we were interested to test for abnormalities in tryptophan metabolism in SLE which may result from activation of indoleamine 2,3-dioxygenase by cytokines released during the immune response. We measured serum tryptophan and kynurenine concentrations in 52 patients with SLE as well as serum neopterin as an indicator for the degree of immune activation. Compared to controls, we found significantly decreased tryptophan and increased kynurenine concentrations in SLE. The extent of tryptophan catabolism correlates with neopterin concentrations or with the disease activity index. Tryptophan depletion may be associated with neurologic/psychiatric disturbances in patients suffering from SLE.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Cowen, P.J., 1996, The serotonin hypothesis: necessary but not sufficient, in: Selective serotonin reuptake inhibitors. (J. Feigher and W. Boyer, eds), 2nd edn. pp. 63–86, John Wiley, Chichester.
Ellenbogen, M.A., Young, S.N., Dean, P., Palmour, R.M., and Benkelfat, C., 1996, Mood response to acute tryptophan depletion in healthy volunteers: Sex differences and temporal stability, Neuropsy-chopharmacology. 15:465–474.
Freese, A., Swartz, K.J., During, M.J., and Martin, J.B., 1990, Kynurenine metabolites of tryptophan: Implications for neurological diseases, Neurology 40:691–695.
Fuchs, D., Hausen, A., Reibnegger, G., Werner, E.R., Dierich, M.P., and Wachter, H., 1988, Neopterin as a marker for activated cell-mediated immunity: application in HIV infection, Immunol. Today, 9:150–155.
Fuchs, D., Möller, A.A., Reibnegger, G., Stöckle, E., Werner, E.R., and Wachter, H., 1990, Decreased serum tryptophan in patients with HIV-1 infection correlates with increased serum neopterin and with neurologic/psychiatric symptoms, J. Acquir. Immune Def. Syndr. 3:873–876.
Gasse, T., Murr, C., Meyersbach, P., Schutzhard, E., Wachter, H., and Fuchs, D., 1994, Neopterin production and tryptophan degradation in acute neuroborreliosis versus late Lyme encephalopathy, Eur. J. C?in. Chem. Clin. Biochem. 32:685–689.
Gasse, T., Widner, B., Baier-Bitterlich, G., Sperner-Unterweger, B., Leblhuber, F., Wachter H., and Fuchs, D., 1998, Abnormal tryptophan metabolism, neurologic/psychiatric disturbances and its relationship to immune activation, in: Progress in HPLC-HPCE: Vol. 7. Neurochemical markers of degenerative diseases and drug addiction, (G.A. Qureshi, H. Parvez, P. Caudy, and S. Parvez, eds), pp. 351–382, VSP Press, Zeist.
Hanly, J.G., 1997, Disease activity, cumulative damage and quality of life in systematic lupus erythematosus: results of a cross-sectional study, Lupus 6:243–247.
Heyes, M.P., Saito, K., Crowley, J.S., Davis, L.E., Demitrack, M.A., Dez, M., Diling, L.A., Elia, I, Kruesi, M.J., and Lackner, A., 1992, Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurological disease, Brain 115:1249–1273.
Hishikawa, T., Tokano, Y., Sekigawa, I., Ando, S., Takasaki, Y., Hashimoto, H., Hirose, S., Okumura, K., Abe, M., and Shirai, T., 1990, HLA-DP+T cells and deficient interleukin-2 production in patients with systemic lupus erythematosus, Clin. Immunol. Immunopathol. 55:285–296.
Hooks, J.J., Jordan, G.W., Cupps, T., Moutsopoulos, H.M., Fauci, A.S., Notkins, A.L. 1982, Multiple interferons in the circulation of patients with systemic lupus erythematosus and vasculitis, Arthritis Rheum. 25:396–400.
Huber, C., Batchelor, J.R., Fuchs, D., Hausen, A., Lang, A., Niederwieser, D., Reibnegger, G., Swetly, P., Troppmair, J., and Wachter, H., 1984, Immune response-associated production of neopterin. Release from macrophages primarily under control of interferon-gamma, J. Exp. Med. 160:310–316.
Launay, J.M., Copel, L., Callebert, J., Corvaia, N., Lepage, E,, Bricaire, F., Saal, F., and Peries, J., 1988, Decreased whole blood 5-hydroxytryptamine (serotonin) in AIDS patients, J. Acquir. Immune Def. Syndr. 1:324–325.
Lim, K.L., Jones, A.C., Brown, N.S., and Powell, R.J. 1993, Urine neopterin as a parameter of disease activity in patients with systemic lupus erythematosus: Comparisons with serum sIL-2R and antibodies to dsDNA, erythrocyte sedimentation rate, and plasma C3, C4, and C3 degradation products, Ann. Rheum. Dis. 52:429–435.
Linker-Israeli, M., 1992, Cytokines abnormalities in human lupus, Clin. Immunol Immunopathol. 63:10–12.
Linker-Israeli, M., Deans, R.J., Wallace, D.J., Prehn, J., Ozeri-Chen, T., and Klinenberg, J.R., 1991, Elevated levels of endogeneous IL-6 in systemic lupus erythematosus. A putative role in pathogenesis, J. Immunol. 147:117–123.
Raziuddin, S., Nur, M., and Al-Waber, A., 1990, Increased circulating HLA-DR+CD4+T cells in systemic lupus erythematosus: Alterations associated with prednisolone therapy, Scand. J. Immunol 31:139–145.
Samsonov, M.Y., Tilz, G.P., Egonorova, O., Reibnegger, G., Balabanova, R.M., Nassonov, E.L., Nassonova, V.A., Wachter, H., and Fuchs, D., 1995, Serum soluble markers of immune activation and disease activity in systemic lupus erythematosus, Lupus 4:29–32.
Steinberg, A.D. and Klinman, D.M., 1989, Pathogenesis of systemic lupus erythematosus, Rheum. Dis. Clin. North Am. 14:25–29.
Stone, T.W., 1993, Neuropharmacology of quinolinic and kynurenic acids. Pharmacol. Rev. 45:309–379.
Takada, Y. and Smith, Q.R., 1991, Blood-brain barrier transport of kynurenines: Implications for brain synthesis and metabolism, J. Neurochem. 56:2007–2017.
Taylor, M.W. and Gensheng, F., 1991, Relationship between interferon-gamma, indoleamin 2,3-dioxygenase, and tryptophan catabolism. FASEB J., 5:2516–2522.
Thomas, S.R., Witting, P.K., and Stocker, R., 1996, 3-Hydroxyanthranilic acid is an efficient, cell-derived coantioxidant for alpha tocoperol, inhibiting human low density lipoprotein and plasma lipid peroxidation, J. Biol. Chem. 20:32714–32721.
Varesio, L., Clayton., M., Blasi, E., Ruffman, R., and Radzioch, D., 1990, Picolinic acid, a catabolite of tryptophan, as the second signal in the activation of IFN-gamma-primed macrophages, J. Immunol. 145:4265–4271.
Via, C. and Handwerger, B., 1992, T-cell and B-cell function in lupus, Curr. Opin. Rheumatol. 4:630–634.
Vogelgesang, S.A., Heyes, M.P., West, S.G. Salazar, A.M., Sfikakis, P.P., Lipnick, R.N., Klipple, G.L., and Tsokos, G.C., 1996, Quinolinic acid in patients with systemic lupus erythematosus and neuropsychiatric manifestations, J. Rheumatol. 23:850–855.
Wachter, H., Fuchs, D., Hausen, A., Reibnegger, G., Weiss, G., Werner, E.R., and Werner-Felmayer, G., 1992, Neopterin: Biochemistry Methods Clinical Application, p. 29, de Gruyter, Berlen.
Widner, B., Werner, E.R., Schennach, H., Wachter, H, and Fuchs D., 1997, Simultaneous measurement of serum tryptophan and kynurenine by HPLC, Clin. Chem. 43:2424–2426.
Young, S.N., Smith, S.E., Phil, R.O., and Ervin, F.R., 1985, Tryptophan depletion causes a rapid lowering of mood in normal males, Psychophamacology 87:173–177.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1999 Springer Science+Business Media New York
About this chapter
Cite this chapter
Widner, B., Sepp, N., Kowald, E., Kind, S., Schmuth, M., Fuchs, D. (1999). Degradation of Tryptophan in Patients with Systemic Lupus Erythematosus. In: Huether, G., Kochen, W., Simat, T.J., Steinhart, H. (eds) Tryptophan, Serotonin, and Melatonin. Advances in Experimental Medicine and Biology, vol 467. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4709-9_71
Download citation
DOI: https://doi.org/10.1007/978-1-4615-4709-9_71
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-7133-5
Online ISBN: 978-1-4615-4709-9
eBook Packages: Springer Book Archive