危重症严重脓毒症患儿细胞因子水平及其与疾病严重程度和死亡率的关系。

Cytokine Levels in Critically Ill Children With Severe Sepsis and Their Relation With the Severity of Illness and Mortality.

机构信息

Division of Pediatric Critical Care, Department of Pediatrics, Advanced Pediatrics Centre, 29751Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

Department of Immunopathology, 29751Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

出版信息

J Intensive Care Med. 2021 May;36(5):576-583. doi: 10.1177/0885066620912989. Epub 2020 Mar 24.

DOI:10.1177/0885066620912989

PMID:32207354

Abstract

OBJECTIVE

To study the baseline cytokine levels and their relation with the severity of illness and mortality in critically ill children with severe sepsis.

DESIGN

Subgroup analysis of a randomized, double-blind, placebo-controlled trial.

SETTING

Pediatric intensive care unit of a tertiary level teaching hospital in India.

PATIENTS

Fifty children with severe sepsis aged 3 months to 12 years.

MATERIAL AND METHODS

Blood was collected at admission for estimation of pro-inflammatory (interleukin 6 [IL-6], IL-12p70, IL-17, and tumor necrotic factor α [TNF-α]) and anti-inflammatory (IL-10 and transforming growth factor β1 [TGF-β1]) cytokines.

PRIMARY OUTCOME

To find out correlation between cytokine levels and severity of illness scores (Pediatric Risk of Mortality [PRISM] III score, Sequential Organ Failure Assessment [SOFA], and Vasoactive-Inotropic Score [VIS]).

SECONDARY OUTCOMES

To compare cytokine levels among survivors and nonsurvivors.

RESULTS

Baseline pro-inflammatory cytokine levels (median [interquartile range]) were IL-6: 189 (35-285) pg/mL, IL-12p: 48 (28-98) pg/mL, IL-17: 240 (133-345) pg/mL, and TNF-α: 296 (198-430) pg/mL; anti-inflammatory cytokine levels were IL-10: 185 (62-395) pg/mL and TGF-β1: 204 (92-290) ng/mL. Pro-inflammatory cytokines showed positive correlation with PRISM III score: IL-6 (Spearman correlation coefficient, ρ = 0.273, = .06), IL-12 (ρ = 0.367, = .01), IL-17 (ρ = 0.197, = .17), and TNF-α (ρ = 0.284, = .05), and anti-inflammatory cytokines showed negative correlation: IL-10 (ρ = -0.257, = .09) and TGF-β (ρ = -0.238, = .11). Both SOFA and VIS also showed weak positive correlation with IL-12 (ρ = 0.32, = .03 and ρ = 0.31, = .03, respectively). Among nonsurvivors (n = 5), the levels of all the measured pro-inflammatory cytokines were significantly higher as compared to survivors, IL-6: 359 (251-499) pg/mL versus 157 (97-223) pg/mL, < .0001, IL-12p70: 167 (133-196) pg/mL versus 66 (30-100) pg/mL, < .0001, IL-17: 400 (333-563) pg/mL versus 237 (122-318) pg/mL, = .009, and TNF-α: 409 (355-503) pg/mL versus 330 (198-415) pg/mL, = .002, respectively.

CONCLUSION

In critically ill children with severe sepsis, pro-inflammatory cytokines (especially IL-12p70) showed a weak positive correlation with severity of illness and were significantly higher among nonsurvivors.

摘要

目的

研究危重病儿童严重脓毒症的基线细胞因子水平及其与疾病严重程度和死亡率的关系。

设计

随机、双盲、安慰剂对照试验的亚组分析。

地点

印度一家三级教学医院的儿科重症监护病房。

患者

50 名年龄在 3 个月至 12 岁的严重脓毒症儿童。

材料和方法

入院时采集血液，以估计促炎细胞因子（白细胞介素 6 [IL-6]、IL-12p70、IL-17 和肿瘤坏死因子 α [TNF-α]）和抗炎细胞因子（IL-10 和转化生长因子 β1 [TGF-β1]）。

主要结果

确定细胞因子水平与疾病严重程度评分（儿科死亡风险 [PRISM] III 评分、序贯器官衰竭评估 [SOFA] 和血管活性-正性肌力评分 [VIS]）之间的相关性。

次要结果

比较幸存者和非幸存者的细胞因子水平。

结果

基线促炎细胞因子水平（中位数[四分位距]）为 IL-6：189（35-285）pg/mL，IL-12p：48（28-98）pg/mL，IL-17：240（133-345）pg/mL和 TNF-α：296（198-430）pg/mL；抗炎细胞因子水平为 IL-10：185（62-395）pg/mL 和 TGF-β1：204（92-290）ng/mL。促炎细胞因子与 PRISM III 评分呈正相关：IL-6（Spearman 相关系数，ρ=0.273， =.06），IL-12（ρ=0.367， =.01），IL-17（ρ=0.197， =.17）和 TNF-α（ρ=0.284， =.05），抗炎细胞因子呈负相关：IL-10（ρ=-0.257， =.09）和 TGF-β（ρ=-0.238， =.11）。SOFA 和 VIS 也与 IL-12 呈弱正相关（ρ=0.32， =.03 和 ρ=0.31， =.03，分别）。在非幸存者（n=5）中，与幸存者相比，所有测量的促炎细胞因子水平均显著升高，IL-6：359（251-499）pg/mL 与 157（97-223）pg/mL， <.0001，IL-12p70：167（133-196）pg/mL 与 66（30-100）pg/mL， <.0001，IL-17：400（333-563）pg/mL 与 237（122-318）pg/mL， =.009，和 TNF-α：409（355-503）pg/mL 与 330（198-415）pg/mL， =.002，分别。