白细胞介素-2在早期急性呼吸窘迫综合征中的作用:与多形核中性粒细胞凋亡及患者生存的关系。

Interleukin-2 involvement in early acute respiratory distress syndrome: relationship with polymorphonuclear neutrophil apoptosis and patient survival.

作者信息

Lesur O, Kokis A, Hermans C, Fülöp T, Bernard A, Lane D

机构信息

Medical and Surgical Intensive Care Units, Université de Sherbrooke, PQ, Canada.

出版信息

Crit Care Med. 2000 Dec;28(12):3814-22. doi: 10.1097/00003246-200012000-00010.

Abstract

OBJECTIVE

To determine blood and lung alveolar concentrations of interleukin (IL)-2 in acute respiratory distress syndrome (ARDS) and their relationship with polymorphonuclear neutrophil (PMN) apoptosis and patient survival.

DESIGN

Prospective cohort study.

SETTING

Medical and surgical intensive care units (ICUs; Canada) and the intensive care department (Belgium).

PATIENTS

Nineteen consecutive patients with ARDS, 14 non-ARDS ICU patients, and 20 healthy volunteers.

INTERVENTIONS

Blood samples and bronchoalveolar lavages (BAL) obtained via venous puncture and by fiberoptic bronchoscopy in the first 72 hrs after the onset of ARDS.

MEASUREMENTS AND MAIN RESULTS

One early point concentration of IL-2 was measured in both blood and BAL fluids of the three groups. In vivo alveolar PMN apoptotic index in BAL fluids and the influence of BAL fluid exposure on normal blood PMN spontaneous apoptosis in vitro were evaluated. Blood IL-2 was significantly lower in patients with ARDS compared with non-ARDS ICU patients and controls. In contrast, IL-2 in BAL fluids of patients with ARDS was dramatically elevated compared with non-ARDS ICU patients and controls. ARDS survivors exhibited lower early IL-2 blood levels than nonsurvivors and generally had a higher IL-2 lung content Lung alveolar PMN apoptosis in vivo was lower in patients with ARDS in comparison with controls. This apoptotic index was correlated with corresponding IL-2 alveolar levels in patients with ARDS. Exposure of normal blood PMN to BAL fluids from patients with ARDS delayed apoptosis in vitro. Immunodepletions of IL-2, granulocyte-macrophage colony stimulating factor, and a combination of both cytokines from BAL fluids of ARDS patients significantly restored PMN apoptosis. The recovery of PMN apoptosis was more effective when IL-2 was depleted in BAL fluids from ARDS survivors compared with nonsurvivors.

CONCLUSIONS

Opposite and disproportional concentrations of IL-2 are observed in blood and lung fluids of patients with early ARDS. IL-2 significantly contributes (with granulocyte-macrophage colony stimulating factor) to the inhibition of PMN apoptosis in BAL fluids of patients with ARDS. Early low blood IL-2 and high IL-2-driven inhibition of PMN apoptosis are beneficial to survivors. Thus, IL-2 is a new candidate for monitoring in early ARDS and an interesting indicator of prognosis.

摘要

目的

测定急性呼吸窘迫综合征(ARDS)患者血液和肺泡中白细胞介素(IL)-2的浓度,以及它们与多形核中性粒细胞(PMN)凋亡和患者生存率的关系。

设计

前瞻性队列研究。

地点

加拿大的内科和外科重症监护病房(ICU)以及比利时的重症监护科。

患者

19例连续的ARDS患者、14例非ARDS的ICU患者和20名健康志愿者。

干预措施

在ARDS发病后的最初72小时内,通过静脉穿刺采集血样,并通过纤维支气管镜进行支气管肺泡灌洗(BAL)。

测量指标及主要结果

测定三组患者血液和BAL液中IL-2的一个早期点浓度。评估BAL液中体内肺泡PMN凋亡指数以及BAL液暴露对体外正常血液PMN自发凋亡的影响。与非ARDS的ICU患者和对照组相比,ARDS患者血液中的IL-2显著降低。相反,与非ARDS的ICU患者和对照组相比,ARDS患者BAL液中的IL-2显著升高。ARDS幸存者早期血液中的IL-2水平低于非幸存者,且肺部IL-2含量通常更高。与对照组相比,ARDS患者体内肺泡PMN凋亡率更低。该凋亡指数与ARDS患者相应的肺泡IL-2水平相关。正常血液PMN暴露于ARDS患者的BAL液中会延迟体外凋亡。从ARDS患者的BAL液中免疫去除IL-2、粒细胞-巨噬细胞集落刺激因子以及这两种细胞因子的组合可显著恢复PMN凋亡。与非幸存者相比,从ARDS幸存者的BAL液中去除IL-2时,PMN凋亡的恢复更有效。

结论

在早期ARDS患者的血液和肺液中观察到IL-2浓度呈相反且不成比例的情况。IL-2(与粒细胞-巨噬细胞集落刺激因子一起)显著促进了ARDS患者BAL液中PMN凋亡的抑制。早期血液中低IL-2水平以及IL-2驱动的对PMN凋亡的高抑制作用对幸存者有益。因此,IL-2是早期ARDS监测的新候选指标,也是一个有趣的预后指标。

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