Stassen Nicole A, Breit Christina M, Norfleet Lisa A, Polk Hiram C
Department of Surgery, Price Institute of Surgical Research, University of Louisville School of Medicine, Louisville, KY 40202, USA.
Surgery. 2003 Aug;134(2):351-6. doi: 10.1067/msy.2003.248.
Interleukin (IL)-18 is a proinflammatory cytokine involved in the regulation of cell-mediated and innate immune responses to infection, trauma, and inflammation. Elevated levels of IL-18 have been noted to correlate with organ dysfunction after injury. This study evaluates the relationship between IL-18 promoter polymorphisms and the development of sepsis after injury.
DNA was extracted from peripheral leukocytes of trauma patients with an injury severity score of 16 or greater. Patient clinical course was followed for the development of sepsis as an endpoint. Two SNPs (-607bp and -137bp) were amplified using polymerase chain reaction. Alleles were identified via agarose gel separation. Genotypes were then determined and correlated with patient data. Postinjury IL-18 levels were determined by enzyme-linked immunoassay.
Sixty-six patients were evaluated; 36 (52%) developed sepsis. Each SNP had 2 alleles and 3 genotypes. The SNP at -607bp had an allelic frequency of 59% for C and 41% for A; whereas -137bp was a G 79% of the time and a C 21% of the time. Individually, each SNP had no direct correlation between the patient's genotype and development of infection. However, when the -607bp CA genotype was combined with the -137bp GC genotype (CA/GC), only 4 patients (27%) developed sepsis (P =.02).
This study supports the conclusion that IL-18 genetic promoter polymorphisms correlate with the development of postinjury sepsis. Further investigation is needed to identify the impact of variation in genotype across a range of genes involved in connected regulatory pathways.
白细胞介素（IL）-18是一种促炎细胞因子，参与对感染、创伤和炎症的细胞介导及固有免疫反应的调节。已注意到IL-18水平升高与损伤后器官功能障碍相关。本研究评估IL-18启动子多态性与损伤后脓毒症发生之间的关系。
从损伤严重程度评分16分或更高的创伤患者外周血白细胞中提取DNA。以脓毒症发生作为终点，跟踪患者的临床病程。使用聚合酶链反应扩增两个单核苷酸多态性（SNP，-607bp和-137bp）。通过琼脂糖凝胶分离鉴定等位基因。然后确定基因型并与患者数据相关联。通过酶联免疫吸附测定法测定损伤后IL-18水平。
评估了66例患者；36例（52%）发生脓毒症。每个SNP有2个等位基因和3种基因型。-607bp处的SNP，C等位基因频率为59%，A为41%；而-137bp处，G出现频率为79%，C为21%。单独来看，每个SNP的患者基因型与感染发生之间均无直接关联。然而，当-607bp的CA基因型与-137bp的GC基因型（CA/GC）结合时，只有4例患者（27%）发生脓毒症（P = 0.02）。
本研究支持IL-18基因启动子多态性与损伤后脓毒症发生相关的结论。需要进一步研究以确定一系列参与相关调节途径的基因中基因型变异的影响。
