体外膜肺氧合治疗对成人暴发性心肌炎患者细胞因子表达谱的影响

Influence of extracorporeal membrane oxygenation therapy on cytokine expression profile in adult patient with fulminant myocarditis

目的:分析暴发性心肌炎患者血清细胞因子表达谱,观察体外膜肺氧合(ECMO)治疗对暴发性心肌炎患者细胞因子水平的影响。方法:纳入暴发性心肌炎患者28例和19例对照者,采集基线和ECMO撤除后的外周血,分离血清,液相芯片分析法检测14种细胞因子水平,观察暴发性心肌炎患者血清细胞因子变化及其对生存结局的预测效能。结果:暴发性心肌炎组和对照组血清中均未检测到白细胞介素-3(IL-3)表达。干扰素-α(IFN-α)、IFN-γ、IL-1α、IL-1β、IL-1ra、IL-4、IL-10、IL-33和血管内皮细胞生长因子(VEGF)水平在暴发性心肌炎组和对照组之间比较差异无统计学意义(均P>0.05)。暴发性心肌炎患者血清IL-2[(5400.00±2181.00)pg/ml]、IL-6[714.6(521.0,1071.0)pg/ml]、IL-7[269.7(169.4,402.5)pg/ml]和IL-15[105.7(50.5,186.5)pg/ml]水平均显著高于对照组(均P<0.05)。暴发性心肌炎组存活者和死亡者血清IL-6水平的受试工作者特征曲线分析示,曲线下面积为0.871,95%可信区间为0.740~1.002,生存结局预测效能良好(P=0.006)。但IL-2、IL-7和IL-15的生存结局预测效能较差(均P>0.05)。暴发性心肌炎存活者血清IL-6水平在ECMO撤除后显著低于基线[337.8(212.5,432.7)pg/ml与635.8(327.4,893.7)pg/ml,P=0.0014],但IL-2、IL-7和IL-15水平在基线和ECMO撤除后的比较差异无统计学意义(均P>0.05)。结论:IL-2、IL-6、IL-7和IL-15可能参与了暴发性心肌炎的发病,ECMO治疗通过降低血清IL-6水平抑制患者炎症应答。

Objective:To analyze serum cytokine expression profile,and to investigate the influence of extracorporeal membrane oxygenation(ECMO)therapy on cytokine expression in patients with fulminant myocarditis.Methods:Twenty-eight patients with fulminant myocarditis and nineteen controls were enrolled.Blood samples were collected at baseline and post ECMO therapy,and serum was isolated.Fourteen cytokine levels in the serum were measured by luminex performance assay.Changes of cytokine levels and prognostic values for survival were assessed.Results:IL-3 was not detected in the serum of either fulminant myocarditis patients or controls.There was no significant difference in serum interferon-α(IFN-α),IFN-γ,interleukin-1α(IL-1α),IL-1β,IL-1ra,IL-4,IL-10,IL-33 or vascular endothelial growth factor level between fulminant myocarditis patients and controls(all P>0.05).The levels of IL-2[(5400.00±2181.00)pg/ml],IL-6[714.6(521.0,1071.0)pg/ml],IL-7[269.7(169.4,402.5)pg/ml]and IL-15[105.7(50.5,186.5)pg/ml]were remarkably increased in fulminant myocarditis patients compared with controls(all P<0.05).Serum IL-6 in survival and death groups of fulminant myocarditis patients was analyzed by receiver operating characteristic curve,and the area under the curve was 0.871,and 95%confidence interval was 0.740 to 1.002,indicating the better prognostic value for survival(P=0.006).However,IL-2,IL-7 or IL-15 had worse prognostic values for survival(all P>0.05).Serum IL-6 level was robustly reduced post ECMO therapy compared with baseline in survival patients of fulminant myocarditis[337.8(212.5,432.7)pg/ml vs.635.8(327.4,893.7)pg/ml,P=0.0014].However,there was no statistical difference in IL-2,IL-7 or IL-15 between baseline and post ECMO therapy(all P>0.05).Conclusion:IL-2,IL-6,IL-7 and IL-15 might take part in the pathogenesis of fulminant myocarditis.ECMO therapy reduced inflammatory response of fulminant myocarditis patients through reduction of IL-6.