Influence of interleukin-10 polymorphisms on interleukin-10 expression and survival in critically ill patients
Influence of interleukin-10 polymorphisms on interleukin-10 expression and survival in critically ill patients
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DOI：
10.1097/00003246-200301000-00005
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发表时间：
2003-01-01
影响因子：
8.8
通讯作者：
Webster, NR
中科院分区：
文献类型：
--
作者：
Lowe, PR;Galley, HF;Webster, NR
Objective.为了确定白细胞介素10基因启动子和上游区域中已鉴定的多态性在从健康志愿者的脂多糖刺激的全血中释放白细胞介素10方面的功能，并评估白细胞介素10多态性与白细胞介素10释放、脓毒症发展和危重患者死亡率的关系。设计：观察性研究。麻醉和重症监护学术单位、大学实验室和一所大学教学医院的10个床位的普通重症监护病房。受试者：总共132名健康志愿者和67名连续危重患者，他们在入院24小时内被招募到重症监护病房，无论诊断如何。采用酶联免疫吸附法测定血浆白细胞介素-10水平。采用限制性片段长度多态性分析检测单核苷酸多态性。二核苷酸重复多态性的确定后，聚合酶链反应使用DNA大小analyzer.Main结果：刺激的白细胞介素-10释放在危重患者显着低于健康受试者（p <0.0001）。此外，在发生脓毒症的患者中，进入重症监护室时的白细胞介素-10释放显著低于随后未发生脓毒症的患者（中位数[范围] 1.47 [0.13-6.90] ng/mL与4.93 [0.03-16.80] ng/mL，p = 0.001）。单核苷酸多态性基因-592碱基对的A等位基因与危重患者白细胞介素-10释放降低和死亡率升高相关。其他多态性与白细胞介素-10释放，脓毒症，或mortality.Conclusions：A等位基因的-592碱基对单核苷酸多态性的白细胞介素-10基因与低刺激白细胞介素-10释放和死亡率增加。需要进一步的研究来确定该标记物的功能性质以及潜在的诊断和治疗方面。
Objective. To determine the functionality of identified polymorphisms in the promoter and upstream regions of the interleukin-10 gene in terms of release of interleukin-10 from lipopolysaccharide-stimulated whole blood from healthy volunteers and to evaluate the relationship of interleukin-10 polymorphisms to interleukin-10 release, development of sepsis, and mortality in critically ill patients.Design: Observational study.Setting: The academic unit of anesthesia and intensive care, university laboratories, and ten-bed general intensive care unit in a university teaching hospital.Subjects: A total of 132 healthy volunteers plus 67 consecutive critically ill patients recruited within 24 hrs of admission to the intensive care unit, regardless of diagnosis.Measurements: Plasma interleukin-10 levels were measured by enzyme-linked immunosorbent assay. Single nucleotide polymorphisms were detected by restriction fragment length polymorphism analysis. Dinucleotide repeat polymorphisms were identified after polymerase chain reaction using a DNA size analyzer.Main Results: Stimulated interleukin-10 release in critically ill patients was significantly lower than in healthy subjects (p < .0001). In addition, in the patients who developed sepsis, interleukin-10 release at admission to the intensive care unit was significantly lower than in patients who did not subsequently develop sepsis (median [range] 1.47 [0.13-6.90] ng/mL compared with 4.93 [0.03-16.80] ng/mL, p = .001). The A allele of the single nucleotide polymorphism at -592 base pairs was associated with lower interleukin-10 release and higher mortality in critically ill patients. Other polymorphisms were not linked to interleukin-10 release, sepsis, or mortality.Conclusions: The A allele of the -592 base pair single nucleotide polymorphism in the interleukin-10 gene is associated with lower stimulated interleukin-10 release and increased mortality. Further investigations are required to determine the nature of the functionality and the potential diagnostic and therapeutic aspects of this marker.