State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Yuzhong District, Chongqing, 400042, PR China.
Crit Care. 2009;13(6):R188. doi: 10.1186/cc8182. Epub 2009 Nov 26.
An excessive inflammatory response is thought to account for the pathogenesis of sepsis and multiple organ dysfunction syndrome (MODS) after severe trauma. The interleukin-10 (IL-10) is a potent anti-inflammatory cytokine. The objectives of this prospective study were to investigate the distribution of IL-10 promoter polymorphisms in a cohort of 308 Chinese Han patients with major trauma, and to identify associations of IL-10 promoter polymorphisms with IL-10 production and incidence of sepsis and MODS.
A total of 308 patients with major trauma were included in this study. The genotypes of polymorphisms -1082, -819 and -592 were determined by polymerase chain reaction-restriction fragment length polymorphism. The IL-10 levels in the supernatants were determined with enzyme-linked immunoabsorbent assay.
The -1082A and -592A alleles were significantly associated with lower lipopolysaccharide-induced IL-10 production in an allele-dose dependent fashion. There was no significant difference for the -819 polymorphism. Except for the -1082 polymorphism, the -819 and -592 polymorphisms were not significantly associated with sepsis morbidity rate and MOD scores.
Our results further confirm the functionality of the IL-10 promoter single nucleotide polymorphisms in relation to IL-10 production. They also suggest that individual difference in IL-10 production in trauma patients might be at least in part related to genetic variations in the IL-10 promoter region.
过度的炎症反应被认为是导致严重创伤后脓毒症和多器官功能障碍综合征(MODS)的发病机制。白细胞介素-10(IL-10)是一种有效的抗炎细胞因子。本前瞻性研究的目的是调查白细胞介素-10 启动子多态性在 308 例中国汉族严重创伤患者中的分布,并确定白细胞介素-10 启动子多态性与白细胞介素-10 产生以及脓毒症和 MODS 的发生率之间的关系。
本研究共纳入 308 例严重创伤患者。通过聚合酶链反应-限制性片段长度多态性确定多态性-1082、-819 和-592 的基因型。采用酶联免疫吸附试验测定上清液中 IL-10 水平。
-1082A 和-592A 等位基因与脂多糖诱导的 IL-10 产生呈等位基因剂量依赖性降低显著相关。-819 多态性无显著差异。除-1082 多态性外,-819 和-592 多态性与脓毒症发病率和 MOD 评分无显著相关性。
我们的结果进一步证实了白细胞介素-10 启动子单核苷酸多态性与 IL-10 产生之间的功能关系。它们还表明,创伤患者中 IL-10 产生的个体差异至少部分与白细胞介素-10 启动子区域的遗传变异有关。