类风湿关节炎患者血液中色氨酸降解增加。

Increased degradation of tryptophan in blood of patients with rheumatoid arthritis.

作者信息

Schroecksnadel Katharina, Kaser Sabine, Ledochowski Maximilian, Neurauter Gabriele, Mur Erich, Herold Manfred, Fuchs Dietmar

机构信息

Institute of Medical Chemistry and Biochemistry, Leopold Franzens University of Innsbruck, Fritz Pregl Strasse 3, A-6020 Innsbruck, Austria.

出版信息

J Rheumatol. 2003 Sep;30(9):1935-9.

PMID:12966593

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 microM, 40.31-49.95 microM) compared to healthy blood donors (62.62 microM, 57.27-74.61 microM; p < 0.001). Kynurenine in patients (1.86 microM, 1.54-2.31 microM) did not differ from controls (2.06 microM, 1.58-2.65 microM; 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.

摘要

目的

干扰素（IFN）-γ激活吲哚胺-（2,3）-双加氧酶（IDO）可导致色氨酸向犬尿氨酸的转化增强。由于慢性免疫激活，色氨酸的可利用性降低，由于蛋白质合成受到影响，导致细胞增殖受到抑制。因此，IDO激活导致的色氨酸剥夺可能有效地消除高代谢周转率的过程，从而调节细胞免疫反应。

方法

采用高效液相色谱法测定38例类风湿关节炎（RA）患者血清中色氨酸、犬尿氨酸和新蝶呤的浓度。计算犬尿氨酸：色氨酸比值（kyn/trp）以评估IDO活性。

结果

与健康献血者（62.62μM，57.27 - 74.61μM；p < 0.001）相比，RA患者的色氨酸浓度较低（中位数，四分位间距：44.95μM，40.31 - 49.95μM）。患者的犬尿氨酸（1.86μM，1.54 - 2.31μM）与对照组（2.06μM，1.58 - 2.65μM；无显著性差异）无差异。患者的kyn/trp比值（42.39 mM/M，37.02 - 48.60 mM/M）高于对照组（31.72 mM/M；27.95 - 35.03 mM/M；p < 0.001）。犬尿氨酸浓度（rs = 0.611；p < 0.001）和kyn/trp比值（rs = 0.621；p < 0.001）与新蝶呤浓度相关，这表明RA患者的细胞免疫反应受到刺激。