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严重烧伤后单核细胞人类白细胞抗原-DR表达降低:与严重程度及继发性脓毒性休克的相关性

Decreased monocyte human leukocyte antigen-DR expression after severe burn injury: Correlation with severity and secondary septic shock.

作者信息

Venet Fabienne, Tissot Sylvie, Debard Anne-Lise, Faudot Caroline, Crampé Carine, Pachot Alexandre, Ayala Alfred, Monneret Guillaume

机构信息

Hospices Civils de Lyon, Hôpital Neurologique, Laboratoire d'Immunologie, Lyon, France.

出版信息

Crit Care Med. 2007 Aug;35(8):1910-7. doi: 10.1097/01.CCM.0000275271.77350.B6.

Abstract

OBJECTIVE

Severe thermal injury causes immune dysfunctions involving both pro- and anti-inflammatory mechanisms. It subsequently leads to a state of immune deficiency that shares some similarities with sepsis-induced immunosuppression. A hallmark of the latter is established by decreased monocyte human leukocyte antigen-DR (mHLA-DR) measurements. The main objective of the current study was to characterize the appearance and the duration of low mHLA-DR expression after severe burn as well as to determine its correlation with mortality and septic complications.

DESIGN

Observational study.

SETTING

Burn unit (intensive care unit) in a university hospital.

PATIENTS

Severe burn patients (total burn surface area >30%, n = 14) and healthy individuals (n = 29).

INTERVENTIONS

None.

MEASUREMENTS AND MAIN RESULTS

Patients were immunologically monitored during 15 days. We quantified mHLA-DR expression with a standardized flow cytometry protocol. Every patient presented with decreased mHLA-DR expression at days 2-3 after burn. Then, from days 4-6, this expression increased in patients who would survive whereas it remained low in nonsurvivors. As early as days 7-10 after burn, patients who were going to develop secondary septic shock exhibited significantly lower mHLA-DR expression in comparison with patients recovering without severe septic complications. Using quantitative reverse transcriptase-polymerase chain reaction, at days 4-6, we found that the RNA level of the nonpolymorphic HLA-DRA chain and the transcription factor class II transactivator were also significantly decreased compared with healthy controls; however, plasma cytokines (interleukin-6, tumor necrosis factor-alpha, and interleukin-10) did not provide any significant prognostic information.

CONCLUSIONS

Severe burn injury induced a marked reduction in mHLA-DR expression at both protein and messenger RNA levels. Its persistent decrease was associated with mortality and the development of septic complications.

摘要

目的

严重热损伤会导致涉及促炎和抗炎机制的免疫功能障碍。随后会引发一种免疫缺陷状态,这与脓毒症诱导的免疫抑制有一些相似之处。后者的一个标志是单核细胞人类白细胞抗原-DR(mHLA-DR)测量值降低。本研究的主要目的是描述严重烧伤后低mHLA-DR表达的出现情况和持续时间,并确定其与死亡率和脓毒症并发症的相关性。

设计

观察性研究。

地点

大学医院的烧伤科(重症监护病房)。

患者

严重烧伤患者(烧伤总面积>30%,n = 14)和健康个体(n = 29)。

干预措施

无。

测量指标及主要结果

对患者进行了15天的免疫监测。我们采用标准化的流式细胞术方案对mHLA-DR表达进行定量。每位患者在烧伤后第2至3天均出现mHLA-DR表达降低。然后,在第4至6天,存活患者的这种表达增加,而未存活患者的表达仍保持在低水平。早在烧伤后第7至10天,与未发生严重脓毒症并发症而康复的患者相比,即将发生继发性脓毒症休克的患者mHLA-DR表达显著降低。使用定量逆转录聚合酶链反应,在第4至6天,我们发现与健康对照相比,非多态性HLA-DRA链和转录因子II类反式激活因子的RNA水平也显著降低;然而,血浆细胞因子(白细胞介素-6、肿瘤坏死因子-α和白细胞介素-10)未提供任何显著的预后信息。

结论

严重烧伤损伤在蛋白质和信使RNA水平均导致mHLA-DR表达显著降低。其持续降低与死亡率和脓毒症并发症的发生相关。

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