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血清吲哚胺 2,3-双加氧酶活性预测社区获得性肺炎的预后。

Serum activity of indoleamine 2,3-dioxygenase predicts prognosis of community-acquired pneumonia.

机构信息

Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.

出版信息

J Infect. 2011 Sep;63(3):215-22. doi: 10.1016/j.jinf.2011.07.003. Epub 2011 Jul 19.

Abstract

OBJECTIVES

Indoleamine 2,3-dioxygenase (IDO) catalyzes the rate-limiting step of tryptophan (Trp) degradation in the kynurenine (Kyn) pathway. By depleting Trp, IDO plays a critical role in inducing immune suppression and tolerance. The aim of present study was to investigate serum IDO activity, determined by Kyn-to-Trp ratio (Kyn/Trp ratio), in community-acquired pneumonia (CAP) and to examine its clinical significance.

METHODS

This study subjects consisted of 129 consecutive patients with CAP and 64 healthy controls. The concentrations of Kyn and Trp were measured simultaneously by liquid chromatography/electrospray ionization tandem mass spectrometry.

RESULTS

The CAP patients had significantly higher Kyn concentrations and significant lower Trp concentrations than the controls (p < 0.0001 and p < 0.0001, respectively). Accordingly, IDO activity was significantly higher (2.4-fold) in the patients than in the controls (p < 0.0001). IDO activity correlated well with PSI (Pneumonia Severity Index) and CURB65 (p = 0.0005 and p < 0.0001, respectively). Moreover, the IDO activity and Kyn concentration were significantly higher in the nonsurvivors and were found to predict mortality in multivariate analysis.

CONCLUSIONS

IDO activity was increased in CAP, and this activity was associated with the severity and outcome of this disease. These results suggest that IDO activity can predict prognosis of CAP.

摘要

目的

色氨酸 2,3-双加氧酶(IDO)催化犬尿氨酸(Kyn)途径中色氨酸(Trp)降解的限速步骤。通过耗尽 Trp,IDO 在诱导免疫抑制和耐受中起关键作用。本研究旨在研究社区获得性肺炎(CAP)患者血清 IDO 活性,并探讨其临床意义。

方法

本研究纳入 129 例连续 CAP 患者和 64 例健康对照者。采用液相色谱/电喷雾串联质谱法同时测定 Kyn 和 Trp 的浓度。

结果

与对照组相比,CAP 患者的 Kyn 浓度显著升高,Trp 浓度显著降低(均 p < 0.0001)。因此,患者的 IDO 活性显著高于对照组(2.4 倍,p < 0.0001)。IDO 活性与 PSI(肺炎严重指数)和 CURB65(p = 0.0005 和 p < 0.0001)均相关。此外,非幸存者的 IDO 活性和 Kyn 浓度显著升高,多因素分析发现这两项指标均可预测死亡率。

结论

CAP 患者的 IDO 活性升高,且该活性与疾病的严重程度和预后相关。这些结果提示 IDO 活性可预测 CAP 的预后。

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