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Increased Degradation of Tryptophan in Blood of Patients with Rheumatoid Arthritis
KATHARINA SCHROECKSNADEL, SABINE KASER, MAXIMILIAN LEDOCHOWSKI, GABRIELE NEURAUTER, ERICH MUR, MANFRED HEROLD, and DIETMAR FUCHS
ABSTRACT.
Objective. Activation of the enzyme indoleamine-(2,3)-dioxygenase (IDO) by interferon (IFN)-g leads to enhanced tryptophan conversion to kynurenine. In consequence of chronic immune activation, tryptophan availability is reduced, leading to inhibition of cell proliferation as protein synthesis is affected. Tryptophan deprivation due to IDO activation could therefore be effective in abrogating processes with high metabolic turnover, thus modulating cellular immune response. Methods. Concentrations of tryptophan, kynurenine, and neopterin were measured by HPLC in the sera of 38 patients with rheumatoid arthritis (RA). The kynurenine:tryptophan ratios (kyn/trp) were calculated to estimate IDO activity. Results. Tryptophan concentrations were lower in patients with RA (median, interquartile range: 44.95 µM, 40.31–49.95 µM) compared to healthy blood donors (62.62 µM, 57.27–74.61 µM; p < 0.001). Kynurenine in patients (1.86 µM, 1.54–2.31 µM) did not differ from controls (2.06 µM, 1.58–2.65 µM; NS). The kyn/trp ratio was higher in patients (42.39 mM/M, 37.02–48.60 mM/M) than in controls (31.72 mM/M; 27.95–35.03 mM/M; p < 0.001). Kynurenine concentrations (rs = 0.611; p < 0.001) and kyn/trp ratios (rs = 0.621; p < 0.001) correlated with neopterin concentrations, which indicate stimulated cellular immune response in patients with RA. Conclusions. The data point to a role of immune activation and Th1-type cytokine INF-g to induce elevated tryptophan degradation in patients with RA. (J Rheumatol 2003;30:1935-9) Key Indexing Terms:
RHEUMATOID ARTHRITIS
From the Institute of Medical Chemistry and Biochemistry, and the Department of Internal Medicine, Leopold Franzens University, and the Ludwig-Boltzmann Institute of AIDS Research, Innsbruck, Austria. Supported by the Austrian Funds Zur Förderung der wissenschaftlichen Forschung, project 14154Med and by the Austrian Federal Ministry of Social Affairs and Generations. K. Schroecksnadel, MD; S. Kaser, MD; G. Neurauter, MSc; D. Fuchs, PhD, Institute of Medical Chemistry and Biochemistry, Leopold Franzens University; M. Ledochowski MD; E. Mur, MD; M. Herold, MD, PhD, Department of Internal Medicine, Leopold Franzens University. Address reprint requests to Dr. D. Fuchs, Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Fritz Pregl Strasse 3, A-6020 Innsbruck, Austria. E-mail: dietmar.fuchs@uibk.ac.at Submitted July 29, 2002; revision accepted January 24, 2003. |