重症手足口病患儿血清炎性细胞因子动态变化与神经源性肺水肿的关系

摘要

目的 探讨重症手足口病(HFMD)患儿血清炎性细胞因子动态变化及其与神经源性肺水肿(NPE)的关系.方法 选择2010年3月至2012年12月89例住院重症HFMD患者,按其是否发生NPE分为神经系统受累组(CNSD)与NPE组,于入院后第1、3和5天采用酶链免疫吸附法检测血清IL-4、IL-10、IL-6、IL-17、肿瘤坏死因子-α(TNF-α)、干扰素-γ(IFN-γ)水平,多因素Logistic回归分析筛选NPE的危险因素.结果 1.NPE组IL-6(F时间=1.876,P=0.177;F交互 =2.192,P=0.145;F组间=7.855,P=0.007)、TNF-α(F时间=13.133,P=0.001;F交互 =0.291,P=0.592;F组间=3.644,P=0.042)、IL-10(F时间=14.580,P=0.001;F交互=2.612,P=0.078;F组间=16.823,P=0.000)、INF-γ(F时间=3.093,P=0.045;F交互=0.513,P=0.600;F组间=20.141,P=0.000)水平显著高于CNSD组.2.TNF-α、IL-10、INF-γ于入院第3天达到高峰.3.年龄(OR=3.383,95％ CI:1.173 ～4.759)、持续发热(OR=4.925,95％ CI:1.758 ～3.794)、血糖(OR=3.465,95％ CI:1.303 ～5.220)、白细胞计数(OR=7.579,95％ CI:2.530 ～ 12.704)及IL-10(OR=1.228,95％ CI:1.007 ～1.523)是重症HFMD发生NPE的危险因素.结论 炎性细胞因子的动态失衡与NPE的发生、发展有关,并可用于评估重症HFMD发生NPE的风险.%Objective To investigate the dynamic changes in the serum inflammatory cytokines and their association with neurogenic pulmonary edema (NPE) in the patients with severe hand-foot-mouth disease (HFMD).Methods Eighty-nine patients with severe HFMD from March 2010 to December 2012 were recruited in the study.The patients were divided into NPE group and central nervous system diseases (CNSD) group according whether they had NPE.The cytokines,including interleukin (IL)-4,IL-6,IL-10,IL-17,tumor necrosis factor-α (TNF-α) and interferon-γ(IFN-γ)were evaluated by using enzyme-linked immunosorbent assay on day 1,3 and 5 after admission to hospital.Risk factors for NPE involvement during hospital stay were analyzed with multivariate Logistic regression analysis.Results (1) Compared with the CNSD group,the serum levels of IL-6 (Ftime =1.876,P =0.177,Ftime* group =2.192,P =0.145,Fgroup =7.855,P =0.007),TNF-α(Ftime =13.133,P =0.001,Ftime* group =0.291,P =0.592,Fgroup =3.644,P =0.042),IL-10 (Ftime =14.580,P =0.001,Ftime* group =2.612,P =0.078,Fgroup =16.823,P =0.000),INF-γ (Ftime =3.093,P =0.045,Ftime* group =0.513,P =0.600,Fgroup =20.141,P =0.000) were significantly higher than those in NPE group.(2)The serum levels of TNF-α,IL-10,INF-γ rose to the peak on the third day.(3) By using multivariate Logistic regression analysis,age (OR =3.383,95％ CI:1.173-4.759),days of fever (OR =4.925,95％ CI:1.758-3.794),hyperglycaemia (OR =3.465,95％ CI:1.303-5.220),leucocytosis (OR =7.579,95 ％ CI:2.530-12.704) and elevation of IL-10 (OR =1.228,95 ％ CI:1.007-1.523) were entered into equation.In the risk evaluation model,these variables remained independent predictors for NPE.Conclusions Abnormal cytokine productions appear to be responsible for the pathogenesis of NPE,and might be an effective tool for predicting NPE in infants with severe HFMD.