γ干扰素、白细胞介素-4在病毒性脑炎和化脓性脑膜炎的表达差异及其对神经系统并发症的诊断效能

Differences in the expressions of IFN-γ,IL-4 in patients with viral encephalitis and suppurative meningitis and their diagnostic efficacy for neurological complications

目的探讨γ干扰素(IFN-γ)、白细胞介素-4(IL-4)及IFN-γ/IL-4在不同类型脑炎脑脊液及血清中的表达差异及其对神经系统并发症的诊断效能。方法纳入2019年3月至2021年3月河北省儿童医院收治的40例病毒性脑炎病儿作为病脑组和40例化脓性脑膜炎病儿纳入化脑组,另选取40例中枢神经系统脱髓鞘疾病病儿作为对照组,分别采集三组病儿的脑脊液和血清标本备用,应用酶联免疫吸附测定(ELISA)对脑脊液和血清中IFN-γ、IL-4及IFN-γ/IL-4含量进行检测,分析IFN-γ、IL-4及IFN-γ/IL-4在不同类型脑炎脑脊液及血清中的表达差异。而后根据病儿有无神经系统并发症再次将其分为有并发症组(n=21)和无并发症组(n=99),采用受试者操作特征曲线(ROC曲线)曲线下面积(AUC)分别评价IFN-γ、IL-4及IFN-γ/IL-4对化脓性脑膜炎发生神经系统并发症的效能的预测价值。结果病脑组病儿脑脊液、血清IFN-γ水平分别为[(9.63±1.04)ng/L、(29.08±3.79)ng/L],均明显高于化脑组[(5.74±1.62)ng/L、(14.73±4.25)ng/L]和对照组[(3.44±0.76)ng/L、(11.13±2.05)ng/L](P<0.05),化脑组高于对照组(P<0.05),且血清中IFN-γ浓度高于脑脊液。化脑组病儿脑脊液、血清IL-4水平分别为[(42.17±5.24)ng/L、(91.05±10.91)ng/L],较病脑组[(21.36±1.73)ng/L、(53.26±8.18)ng/L]和对照组[(9.76±1.15)ng/L、(40.08±4.63)ng/L]均偏高(P<0.05),病脑组高于对照组(P<0.05),血清中IL-4含量较脑脊液偏高。病脑组脑脊液和血清中IFN-γ/IL-4最高0.51±0.05、0.49±0.12,化脑组最低0.38±0.06、0.29±0.03,三组组间对比数据差异有统计学意义(P<0.05)。有并发症组病儿脑脊液和血清中IFN-γ[(7.73±0.83)ng/L、(25.13±3.17)ng/L]、IL-4[(38.83±2.35)ng/L、(73.48±7.67)ng/L]及IFN-γ/IL-4(0.42±0.03、0.43±0.09)水平均明显高于无并发症组[(4.15±0.58)ng/L、(12.56±2.08)ng/L、(16.77±4.12)ng/L、(60.13±4.33)ng/L、0.21±0.04、0.19±0.07](均P<0.05)。ROC曲线研究结果显示,IFN-γ、IL-4、IFN-γ/IL-4及联合检测的AUC分别为0.84[95%CI:(0.72,0.96)]、0.87[95%CI:(0.76,0.97)]、0.76[95%CI:(0.62,0.90)]、0.93[95%CI:(0.85,1.00)],三项指标联合诊断的AUC显著高于各项指标单因子预测(P<0.05)。预测价值:联合检测>IL-4>IFN-γ>IFN-γ/IL-4。结论IFN-γ、IL-4及IFN-γ/IL-4在病毒性脑炎和化脓性脑膜炎病儿脑脊液和血清中的表达水平明显升高,且均为血清中水平高于脑脊液中;检测其水平可辅助临床更好地诊断神经系统并发症的发生。

Objective To investigate the expression differences of interferon-γ(IFN-γ),interleukin-4(IL-4)and IFN-γ/IL-4 in cerebrospinal fluid and serum of different types of meningitis and their diagnostic efficacy for nervous system complications.Methods Forty children with viral encephalitis admitted to Hebei Children's Hospital from March 2019 to March 2021 were included as the diseased brain group and 40 cases with suppurative meningitis into the chemical brain group,and another 40 cases with demyelinating diseases of central nervous system were selected as the control group.Cerebrospinal fluid and serum samples were collected from the three groups respectively.The levels of IFN-γ,IL-4 and IFN-γ/IL-4 in cerebrospinal fluid and serum were determined by enzyme-linked immunosorbent assay(ELISA),and the expression differences of IFN-γ,IL-4 and IFN-γ/IL-4 in cerebrospinal fluid and serum of different types of encephalitis were analyzed.The patients were then assigned into a complication group(n=21)and a non-complication group(n=99)according to the presence or absence of neurological complications.Area under receiver operating curve(ROC curve)(AUC)was used to evaluate the predictive value of IFN-γ,IL-4 and IFN-γ/IL-4 on the neurological complications of suppurative meningitis,re‑group were significantly higher than those in the chemical brain group[(5.74±1.62)ng/L,(14.73±4.25)ng/L]and the control group[(3.44±0.76)ng/L,(11.13±2.05)ng/L](P<0.05).The levels of IFN-γin the chemical brain group were significantly higher than those in the control group(P<0.05),and the concentration of IFN-γin serum was higher than that in cerebrospinal fluid.The levels of cerebrospinal fluid and serum IL-4[(42.17±5.24)ng/L,(91.05±10.91)ng/L]in the chemical brain group were were higher than those in the diseased brain group[(21.36±1.73)ng/L,(53.26±8.18)ng/L]and the control group[(9.76±1.15)ng/L,(40.08±4.63)ng/L](P<0.05),and the serum level of IL-4 in the diseased brain group was higher than that in the control group(P<0.05).The serum IL-4 level was higher than the cerebrospinal IL-4 level.The highest levels of IFN-γ/IL-4 in cerebrospinal fluid and serum of the diseased brain group were(0.51±0.05)and(0.49±0.12),and the lowest were(0.38±0.06)and(0.29±0.03)in the chemical brain group,and the differences among the three groups were statistically significant(P<0.05).The levels of IFN-γand IL-4 in cerebrospinal fluid and serum[(7.73±0.83)ng/L,(25.13±3.17)ng/L,(38.83±2.35)ng/L,(73.48±7.67)ng/L]and the level of IFN-γ/IL-4[(0.42±0.03),(0.43±0.09)]in the complication group were significantly higher than those in the non-complication group[(4.15±0.58)ng/L,(12.56±2.08)ng/L,(16.77±4.12)ng/L,(60.13±4.33)ng/L,(0.21±0.04),and(0.19±0.07)](all P<0.05).ROC curve study results showed that the AUCs of IFN-γ,IL-4,IFN-γ/IL-4 and combined tests were 0.84[95%CI:(0.72,0.96)],0.87[95%CI:(0.76,0.97)],0.76[95%CI:(0.62,0.90)],0.93[95%CI:(0.85,1.00)];the AUC of the combined tests of these three indexes was significantly higher than that of the single factor prediction of each index,and the difference was statistically significant(P<0.05).The predictive values ranked from high to low were combined detection,IL-4,IFN-γ,and IFN-γ/IL-4.Conclusion The expression levels of IFN-γ,IL-4,and IFN-γ/IL-4 are significantly elevated in the cerebrospinal fluid and serum of patients with viral encephalitis and purulent meningitis,and the levels in serum were higher than those in cerebrospinal fluid;the detection of its level could assist in the clinical diagnosis of nervous system complications.