Programmed death-1 levels correlate with increased mortality, nosocomial infection and immune dysfunctions in septic shock patients.
Programmed death-1 levels correlate with increased mortality, nosocomial infection and immune dysfunctions in septic shock patients.
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DOI：
10.1186/cc10112
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Venet F
中科院分区：
文献类型：
--
作者：
Guignant C;Lepape A;Huang X;Kherouf H;Denis L;Poitevin F;Malcus C;Chéron A;Allaouchiche B;Gueyffier F;Ayala A;Monneret G;Venet F
感染性休克仍然是世界范围内的主要卫生保健问题。脓毒症诱导的免疫改变被认为在患者死亡率和医院感染易感性中发挥重要作用。程序性死亡-1（PD-1）受体系统构成了一种新描述的免疫调节途径，负性控制免疫应答。最近已经表明，PD-1敲除小鼠在响应实验性脓毒症时表现出较低的死亡率。本研究的目的是研究感染性休克患者PD-1相关分子的表达。这项前瞻性和观察性研究包括64名感染性休克患者，13名创伤患者和49名健康个体。通过流式细胞术测量循环白细胞上的PD-1相关分子表达。血浆白细胞介素（IL）-10浓度以及离体丝裂原诱导的淋巴细胞增殖进行了评估。我们观察到，与创伤患者和健康志愿者相比，脓毒性休克患者在休克发作后1-2天和3-5天显示PD-1、PD-L1和PD-L2单核细胞表达增加，PD-1和PD-L1 CD 4 + T淋巴细胞表达增加。重要的是，表达增加与继发性院内感染的发生率增加和感染性休克后死亡率增加以及有丝分裂原诱导的淋巴细胞增殖减少和循环IL-10浓度增加相关。这些发现表明PD-1相关分子可能构成了一种新的免疫调节系统，参与脓毒症诱导的免疫改变。结果应在更大的患者队列中得到证实。这可能为治疗这种迄今为止致命的疾病提供创新的治疗观点。
Septic shock remains a major health care problem worldwide. Sepsis-induced immune alterations are thought to play a major role in patients' mortality and susceptibility to nosocomial infections. Programmed death-1 (PD-1) receptor system constitutes a newly described immunoregulatory pathway that negatively controls immune responses. It has recently been shown that PD-1 knock-out mice exhibited a lower mortality in response to experimental sepsis. The objective of the present study was to investigate PD-1-related molecule expressions in septic shock patients. This prospective and observational study included 64 septic shock patients, 13 trauma patients and 49 healthy individuals. PD-1-related-molecule expressions were measured by flow cytometry on circulating leukocytes. Plasmatic interleukin (IL)-10 concentration as well as ex vivo mitogen-induced lymphocyte proliferation were assessed. We observed that septic shock patients displayed increased PD-1, PD-Ligand1 (PD-L1) and PD-L2 monocyte expressions and enhanced PD-1 and PD-L1 CD4+ T lymphocyte expressions at day 1-2 and 3-5 after the onset of shock in comparison with patients with trauma and healthy volunteers. Importantly, increased expressions were associated with increased occurrence of secondary nosocomial infections and mortality after septic shock as well as with decreased mitogen-induced lymphocyte proliferation and increased circulating IL-10 concentration. These findings indicate that PD-1-related molecules may constitute a novel immunoregulatory system involved in sepsis-induced immune alterations. Results should be confirmed in a larger cohort of patients. This may offer innovative therapeutic perspectives on the treatment of this hitherto deadly disease.
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影响因子：
4.4
作者：
Chemnitz, JM;Parry, RV;Riley, JL
通讯作者：
Riley, JL
DOI：
10.1186/cc5055
发表时间：
2006
期刊：
Critical care (London, England)
影响因子：
--
作者：
Cavaillon JM;Adib-Conquy M
通讯作者：
Adib-Conquy M
DOI：
10.1073/pnas.0809422106
发表时间：
2009-04-14
影响因子：
11.1
作者：
Huang, Xin;Venet, Fabienne;Ayala, Alfred
通讯作者：
Ayala, Alfred
影响因子：
30.5
作者：
Latchman, Y;Wood, CR;Freeman, GJ
通讯作者：
Freeman, GJ
影响因子：
4.4
作者：
Monneret, G;Finck, ME;Lepape, A
通讯作者：
Lepape, A