Genomic polymorphism within the TNF and IL-10 locus influences outcome of patients undergoing liver resection.

<背景>胆道恶性肿瘤的大肝脏切除术可诱发系统性炎症反应和脓毒性并发症，导致器官功能障碍。这种疾病的介质是细胞因子肿瘤坏死因子(TNF)- α和白细胞介素。TNF和IL-10基因的基因组多态性可能与大手术后TNF- α和IL-10水平升高和高发病率有关。<患者和方法>我们评估了选择性肝脏手术患者中TNF和IL-10基因双等位基因多态性与促炎和抗炎细胞因子释放和术后脓毒性并发症的关系。在100例未选择的连续肝切除术患者中研究了TNF基因型、TNF- α、IL-10的血浆浓度和脓毒性并发症。采用固相微序列法测定TNF和IL-10基因型。与TNFB1等位基因纯合或杂合的患者相比，TNFB2等位基因纯合的患者tnf - α和白细胞介素-6的峰值浓度更高（n = 53）。TNFB2纯合子术后脓毒性并发症和术后器官功能障碍发生率较高。TNFB2等位基因纯合子的患者可能会在心脏手术后产生增强的全身炎症反应，并增加心肺疾病的风险。IL-10基因型也与术后脓毒性并发症相关。结论肿瘤坏死因子（TNF）和IL-10的>基因多态性与胆道恶性肿瘤肝切除术患者术后脓毒症并发症和器官功能障碍的风险增加有关。

<Background> Major liver resection for biliary malignancy induces a systemic inflammatory response characterized and septic complications resulting in organ dysfunction. Mediators for this morbidity are the cytokines tumor necrosis factor (TNF)-alpha and interleukins. Genomic polymorphism within the TNF and IL10 genes may be associated with increased TNF-alpha and IL-10 levels and high morbidity following major surgery.<Patients and Methods> We assessed the relationship of biallelic polymorphisms of the TNF and IL-10 genes in patients undergoing elective liver surgery to release of proinflammatory and anti-inflammatory cytokines and postoperative septic complications. TNF genotypes, plasma concentrations of TNF-alpha, IL-10, and septic complications were studied in 100 unselected, consecutive patients undergoing liver resection. TNF and IL-10 genotypes were determined by the solid-phase minisequencing method.<Results>Patients homozygous for the TNFB2 allele displayed larger peak concentrations of TNF-alpha and interleukin-6 when compared with patients homozygous or heterozygous for TNFB1 (n = 53). The TNFB2 homozygotes had a higher incidence of postoperative septic complications, and postoperative organ dysfunction. Patients homozygous for the TNFB2 allele may develop an enhanced systemic inflammatory response with an increased risk of cardiopulmonary morbidity after cardiac surgery. IL-10 genotypes were also correlated with postoperative septic complications.<Conclusions> Gene polymorphism of tumor necrosis factor (TNF) and IL-10 were associated with an increased risk of developing postoperative septic complications and organ dysfunction in patients undergoing liver resection for biliary malignancy.