PROGRAMMED DEATH 1 EXPRESSION AS A MARKER FOR IMMUNE AND PHYSIOLOGICAL DYSFUNCTION IN THE CRITICALLY ILL SURGICAL PATIENT
PROGRAMMED DEATH 1 EXPRESSION AS A MARKER FOR IMMUNE AND PHYSIOLOGICAL DYSFUNCTION IN THE CRITICALLY ILL SURGICAL PATIENT
复制标题
DOI：
10.1097/shk.0b013e31825de6a3
复制
发表时间：
2012-08-01
期刊：
影响因子：
3.1
通讯作者：
Heffernan, Daithi S.
中科院分区：
文献类型：
--
作者：
Monaghan, Sean F.;Thakkar, Rajan K.;Heffernan, Daithi S.
程序性死亡1（PD-1）是免疫系统的抑制蛋白受体，并且已显示在危重病的动物模型以及创伤后和人类烧伤受害者中上调。据信，PD-1可能在外科危重病中观察到的免疫功能障碍中发挥作用。然而，尽管先前的研究将PD-1表达的变化与免疫细胞功能的改变相关联，但尚不清楚是否与临床状态存在相关性。因此，我们的目的是描述PD-1在重症创伤和手术患者中观察到的免疫功能障碍中的潜在作用。这是一项观察性队列研究。急性生理学和慢性健康评估II（APACHE II）评分计算了来自三级护理/I级创伤中心的危重和创伤和外科重症监护室患者。在确诊和入住重症监护室后24小时内抽血，以测量循环细胞因子水平以及循环细胞上的PD-1表达。主要观察指标包括白细胞上PD-1表达与生理功能障碍的关系（APACHE II）以及严重生理功能障碍患者中PD-1表达与白细胞介素10水平的相关性。样本收集自90名外科危重患者。在具有严重生理功能障碍（APACHE II >20）的患者中，具有PD-1表达的粒细胞（中值，144 vs. 90个细胞/μ L; P = 0.037）和单核细胞（中值，12 vs. 6个细胞/μ L; P = 0.022）的数量增加。此外，在APACHE II评分大于20的患者中，表达PD-1的CD 3（+）细胞百分比更高（44% vs. 29%; P = 0.015）。当仅评估APACHE II评分大于20的患者时，单核细胞上的PD-1表达与血清中的白细胞介素水平呈正相关（r = 0.525，P = 0.05）。PD-1在危重外科疾病中白细胞表达的变异性与生理功能障碍相关，表明PD-1可能是评估创伤或严重手术损伤后免疫功能障碍的有价值的工具。
Programmed death 1 (PD-1) is an inhibitor protein receptor for the immune system and has been shown to be upregulated in animal models of critical illness as well as after trauma and in burn victims in humans. It is believed that PD-1 may play a role in the immune dysfunction seen in surgical critical illness. However, although prior studies have associated changes in PD-1 expression with altered immune cell function, it is not known if a correlation with clinical status exists. We therefore aimed to describe a potential role for PD-1 in the immune dysfunction seen in critically ill trauma and surgical patients. This is an observational cohort study. Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were calculated on critically ill and injured trauma and surgical intensive care unit patients from a tertiary care/level I trauma center. Blood was drawn within 24 h of establishment of diagnosis and admission to the intensive care unit to measure circulating cytokine levels, as well as PD-1 expression on circulating cells. Main outcome measures included PD-1 expression on leukocytes and the relationship to physiological dysfunction (APACHE II) as well as the correlation of PD-1 expression and interleukin 10 levels among patients with severe physiological dysfunction. Samples were collected from 90 critically ill surgical patients. Among patients with severe physiological dysfunction (APACHE II >20), there were increased numbers of granulocytes (median, 144 vs. 90 cells/mu L; P = 0.037) and monocytes (median, 12 vs. 6 cells/mu L; P = 0.022) with PD-1 expression. In addition, among patients with an APACHE II score of greater than 20, there was a larger percentage of CD3(+) cells (44% vs. 29%; P = 0.015) expressing PD-1. When only patients with an APACHE II score greater than 20 were assessed, PD-1 expression on monocytes correlated positively with interleukin levels in the serum (r = 0.525, P = 0.05). Variability in the expression of PD-1 on leukocytes in critical surgical illness correlates with physiological dysfunction and suggests that PD-1 may be a valuable tool in the assessment of immune dysfunction following trauma or severe surgical insult.