Service des Maladies Infectieuses et Réanimation Médicale, CHU Pontchaillou, rue Henri le Guilloux, 35033 Rennes, France.
J Infect Dis. 2010 Mar 15;201(6):956-66. doi: 10.1086/650996.
Severe sepsis results in a sustained deleterious immune dysregulation. Indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme of tryptophan catabolism, plays a pivotal role in immune tolerance and is induced during various inflammatory conditions.
Plasma samples obtained from patients with septic shock (n = 38), severe sepsis (n = 35), or sepsis (n = 10) and from healthy donors (n = 26) were analyzed for IDO activity by high-performance liquid chromatography. Lymphocyte, monocyte, and regulatory T cell counts as well as monocytic human leukocyte antigen DR (HLA-DR) expression were quantified by flow cytometry. Peripheral blood mononuclear cells and purified CD14(+) and CD14(-) fractions were assayed in vitro for spontaneous and inducible IDO expression and activity.
IDO activity gradually increased according to sepsis severity, and septic patients who died had higher IDO activity on admission than did survivors (P = .013). Monocytes were a major source of active IDO in normal peripheral blood. The percentage and absolute number of circulating CD14(+) cells were increased in septic patients, and their monocytes remained fully able to produce functional IDO after NF-kappaB-independent interferon gamma stimulation but not through NF-kappaB-dependent Toll-like receptor engagement.
IDO activity is increased during severe sepsis and septic shock and is associated with mortality. IDO production could be used to better characterize monocyte reprogramming in sepsis.
严重脓毒症会导致持续的免疫调节功能障碍。吲哚胺 2,3-双加氧酶（IDO）是色氨酸分解代谢的限速酶，在免疫耐受中起关键作用，并且在各种炎症情况下都会被诱导产生。
通过高效液相色谱法分析脓毒性休克（n = 38）、严重脓毒症（n = 35）或脓毒症（n = 10）患者和健康供体（n = 26）的血浆样本中的 IDO 活性。通过流式细胞术定量淋巴细胞、单核细胞和调节性 T 细胞计数以及单核细胞人白细胞抗原 DR（HLA-DR）表达。通过体外测定外周血单核细胞和纯化的 CD14(+)和 CD14(-) 级分的自发和诱导 IDO 表达和活性。
IDO 活性根据脓毒症严重程度逐渐增加，入院时死亡的脓毒症患者的 IDO 活性高于幸存者（P =.013）。单核细胞是正常外周血中活性 IDO 的主要来源。脓毒症患者循环 CD14(+)细胞的百分比和绝对数增加，其单核细胞在 NF-kappaB 非依赖性干扰素 γ刺激后仍能完全产生功能性 IDO，但不能通过 NF-kappaB 依赖性 Toll 样受体结合。
在严重脓毒症和脓毒性休克期间 IDO 活性增加，并与死亡率相关。IDO 的产生可以用来更好地描述脓毒症中单核细胞的重编程。
