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早期白细胞介素-6 和单核细胞人类白细胞抗原-DR 斜率:预测重大创伤后脓毒症发展的有力关联。

Early interleukin-6 and slope of monocyte human leukocyte antigen-DR: a powerful association to predict the development of sepsis after major trauma.

机构信息

Service de réanimation, Hôpital Edouard Herriot-Hospices Civils de Lyon, Lyon, France.

出版信息

PLoS One. 2012;7(3):e33095. doi: 10.1371/journal.pone.0033095. Epub 2012 Mar 14.

Abstract

OBJECTIVE

Major trauma is characterized by a pro-inflammatory response, followed by an immunosuppression. Recently, in trauma patients, the lack of recovery of monocyte Human Leukocyte Antigen DR (mHLA-DR, a biomarker of ICU-acquired immunosuppression) between days 1-2 and days 3-4 has been demonstrated to be independently associated with sepsis development. The main objective of this study was to determine whether early measurements of IL-6 (interleukin-6) and IL-10 plasma concentrations (as markers of initial severity) could improve, in association with mHLA-DR recovery, the prediction of sepsis occurrence in severe trauma patients.

DESIGN

Prospective observational study over 24 months in a Trauma ICU at university hospital.

PATIENTS

Trauma patients with an ISS over 25 and age over 18 were included.

MEASUREMENTS AND MAIN RESULTS

mHLA-DR was assessed by flow cytometry, IL-6 and IL-10 concentrations by ELISA. 100 consecutive severely injured patients were monitored (mean ISS 37±10). 37 patients developed sepsis. IL-6 concentrations and slope of mHLA-DR expression between days 1-2 and days 3-4 were significantly different between septic and non-septic patients. IL-10 was not detectable in most patients. After adjustment for usual clinical confounders, when assessed as a pair, multivariate logistic regression analysis revealed that a slope of mHLA-DR expression (days 3-4/days 1-2)≤1.1 and a IL-6 concentration ≥ 67.1 pg/ml remained highly associated with the development of sepsis (adjusted OR 18.4, 95% CI 4.9; 69.4, p = .00002).

CONCLUSIONS

After multivariate regression logistic analysis, when assessed as a pair, a high IL-6 concentration and a persistent mHLA-DR decreased expression were found to be in relation with the development of sepsis with the best predictive value. This study underlines the usefulness of daily monitoring of immune function to identify trauma patients at a high risk of infection.

摘要

目的

严重创伤的特征是促炎反应,随后是免疫抑制。最近,在创伤患者中,第 1-2 天和第 3-4 天之间单核细胞人类白细胞抗原 DR(单核细胞 HLA-DR,ICU 获得性免疫抑制的生物标志物)恢复不足与脓毒症的发生独立相关。本研究的主要目的是确定早期测量白细胞介素-6(IL-6)和白细胞介素-10 血浆浓度(作为初始严重程度的标志物)是否可以与 mHLA-DR 恢复一起改善,预测严重创伤患者发生脓毒症。

设计

在大学医院的创伤 ICU 进行了为期 24 个月的前瞻性观察研究。

患者

纳入 ISS 超过 25 岁且年龄超过 18 岁的创伤患者。

测量和主要结果

通过流式细胞术评估 mHLA-DR,通过 ELISA 评估 IL-6 和 IL-10 浓度。监测了 100 名连续严重受伤患者(平均 ISS 37±10)。37 名患者发生脓毒症。第 1-2 天和第 3-4 天之间的 IL-6 浓度和 mHLA-DR 表达斜率在脓毒症和非脓毒症患者之间存在显著差异。大多数患者未检测到 IL-10。在调整了通常的临床混杂因素后,当作为一对进行多变量逻辑回归分析时,发现 mHLA-DR 表达斜率(第 3-4 天/第 1-2 天)≤1.1 和 IL-6 浓度≥67.1pg/ml 与脓毒症的发生高度相关(调整后的 OR 18.4,95%CI 4.9;69.4,p=0.00002)。

结论

经过多变量回归逻辑分析,当作为一对进行评估时,发现高 IL-6 浓度和持续的 mHLA-DR 表达减少与脓毒症的发生有关,具有最佳的预测价值。这项研究强调了日常监测免疫功能以识别感染风险高的创伤患者的有用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24e5/3303782/d0832e9f9195/pone.0033095.g001.jpg

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