Department of Internal Medicine, Tampere University Hospital, University of Tampere Medical School, University of Tampere, Tampere, Finland.
Shock. 2010 Feb;33(2):149-54. doi: 10.1097/SHK.0b013e3181ad3195.
Indoleamine 2,3-dioxygenase (IDO), which is the rate-limiting enzyme for tryptophan (trp) catabolism, may play a critical role in various inflammatory disorders. Recent studies on trauma patients have suggested that the degradation of trp is associated with the development of sepsis. The role of IDO activity in bacteremic patients is unclear. We studied IDO activity in 132 patients with bacteremia caused by Staphylococcus aureus, Streptococcus pneumoniae, beta-hemolytic streptococcae, or Eschericia coli. The serum concentrations of trp and its metabolite kynurenine (kyn) were measured by reverse-phase high-performance liquid chromatography 1 to 4 days after the positive blood culture and on recovery. The kyn-to-trp ratio (kyn/trp), reflecting the activity of the IDO enzyme, was calculated. The maximum value in the ratio for every patient during 1 to 4 days after positive blood culture was used in analysis. The maximum kyn/trp ratio was significantly higher in nonsurvivors versus those who survived (193.7 vs. 82.4 micromol/mmol; P = 0.001). The AUC(ROC) of maximal kyn/trp in the prediction of case fatality was 0.75 (95% confidence interval, 0.64-0.87), and the kyn/trp ratio at a cutoff level of 120 micromol/mmol showed 83% sensitivity and 69% specificity for fatal disease. A kyn/trp ratio greater than 120 micromol/mmol was associated with increased risk of death versus low (<or=120 micromol/mmol) ratios (odds ratio, 10.8; confidence interval, 3.0-39.8). High IDO activity also remained an independent risk factor for case fatality in a multivariate model adjusted for potential confounders. The data in this report demonstrate that IDO activity is markedly increased in bacteremia patients, constituting an independent predictor of severe disease and case fatality.
色氨酸（trp）分解代谢的限速酶吲哚胺 2,3-双加氧酶（IDO）可能在各种炎症性疾病中起关键作用。最近对创伤患者的研究表明，trp 的降解与脓毒症的发展有关。IDO 活性在菌血症患者中的作用尚不清楚。我们研究了 132 例金黄色葡萄球菌、肺炎链球菌、β-溶血性链球菌或大肠杆菌引起菌血症患者的 IDO 活性。用反相高效液相色谱法在血培养阳性后 1 至 4 天和恢复时测定血清 trp 及其代谢产物犬尿氨酸（kyn）的浓度。计算犬尿氨酸/色氨酸比值（kyn/trp），反映 IDO 酶的活性。每个患者在血培养阳性后 1 至 4 天内的比值最大值用于分析。存活者与非存活者的最大 kyn/trp 比值差异有统计学意义（193.7 对 82.4μmol/mmol；P = 0.001）。最大 kyn/trp 在预测病死率的 ROC 曲线下面积为 0.75（95%置信区间，0.64-0.87），kyn/trp 比值截断值为 120μmol/mmol 时，对致死性疾病的敏感性为 83%，特异性为 69%。kyn/trp 比值大于 120μmol/mmol 与死亡风险增加相关（比值比，10.8；95%置信区间，3.0-39.8）。在调整潜在混杂因素的多变量模型中，高 IDO 活性仍是病死率的独立危险因素。本报告的数据表明，IDO 活性在菌血症患者中显著增加，是严重疾病和病死率的独立预测因子。
