炎性细胞因子TNF-α、IL-6、IL-8预测新发脑出血患者预后的价值

The value of inflammatory cytokines(TNF⁃α,IL⁃6 and IL⁃8)in predicting prognosis in patients with new⁃onset intracerebral hemorrhage

目的:探讨脑出血患者脑脊液中肿瘤坏死因子a(tumor necrosis factor-α,TNF-α)、白介素6(Interleukin-6,IL-6)、IL-8水平与病情严重程度的关系和预测患者预后的价值。方法:收集2023年3月至2023年12月间新疆军区总医院神经外科收治的40例新发脑出血患者(发病24 h内入院),另选取同期40例患者作为对照组(对照组患者为存在临床症状而于本院接受脑脊液检查者,但最终排除中枢神经系统疾病)。分别采集入院首次脑脊液和血清标本,收集研究对象的临床资料和实验室检测结果(血清、脑脊液样本中炎性细胞因子TNF-α、IL-6、IL-8水平)。根据入院时格拉斯哥昏迷(Glasgow coma scale,GCS)评分将患者分为轻中度组(GCS 9~15分,14例)和重度组(GCS 3~8分,26例);按照出血量分为≥30 mL组(21例)和<30 mL组(19例)。根据脑出血患者出院后90 d的格拉斯哥预后评分(Glasgow out-come scale,GOS),将脑出血患者分为预后良好组(GOS 4~5分,18例)和预后不良组(GOS 1~3分,22例)。采用Spearman相关系数相关性分析和受试者操作特征(receiver operating characteristic,ROC)曲线分析血清、脑脊液中炎性细胞因子预测脑出血患者预后的价值。结果:与对照组比较,脑出血组血清、脑脊液中TNF-α、IL-6和IL-8水平均显著升高(P<0.001),重度脑出血组血清、脑脊液中TNF-α、IL-6和IL-8水平高于轻中度组(P<0.01),且与GCS评分均呈负相关(r=-0.397、P<0.05;r=-0.587、P<0.01;r=-0.615、P<0.01;r=-0.696、P<0.01;r=-0.671、P<0.01;r=-0.510、P<0.01)。与出血量<30 mL组患者相比,≥30 mL组患者的脑脊液中TNF-α、IL-6、IL-8水平均升高(P<0.05),但在血清中仅IL-6水平升高(P<0.05)。预后不良组血清和脑脊液中的TNF-α、IL-6和IL-8水平较预后良好组升高(P<0.01)。ROC曲线分析显示,脑出血患者入院24 h内脑脊液中TNF-α、IL-6、IL-8单项和联合检测预测脑出血患者预后的曲线下面积(area under the receiver operating characteristic curve,AUC)分别为0.836、0.773、0.849、0.917,患者入院24 h内血清TNF-α、IL-6、IL-8单项和联合检测预测脑出血患者预后的AUC分别为0.692、0.808、0.721、0.843。结论:脑出血患者脑脊液中TNF-α、IL-6和IL-8水平升高,且与患者病情严重程度相关。入院24 h内脑脊液中这些指标的水平可能可以用于预测其出院后90 d的预后。

Objective To investigate correlation of levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and IL-8 in cerebrospinal fluid with the severity of the disease in patients with intracerebral hemorrhage,and to analyze the value of the cytokines for predicting prognosis of the patients.Methods A total of 40 patients with new-onset intracerebral hemorrhage,admitted to the Department of Neurosurgery of the General Hospital of Xinjiang Military Region,were collected from March 2023 to December 2023.Forty patients who underwent cerebrospinal fluid examination at the hospital due to the presence of clinical symptoms,but whose central nervous system disease was eventually excluded,served as the control group.Within 24 h of the onset of illness,the patient′s cerebrospinal fluid was collected,as well as the laboratory test re-sults.The levels of inflammatory cytokines TNF-α,IL-6,and IL-8 were measured both in serum and cerebrospinal fluid samples.Patients were divided into the mild-moderate group(GCS 9-15,n=14)and severe group(GCS 3-8,n=26)accor-ding to the Glasgow coma scale(GCS)on admission,and also were divided into≥30mL group(n=21)and<30mL group(n=19)according to the hemorrhage volume.At 90 days after discharge,the patients with intracerebral hemorrhage were di-vided into a good prognosis group(GOS 4-5 points,n=18)and a poor prognosis group(GOS 1-3 points,n=22)according to the Glasgow out-come scale(GOS).Spearman correlation coefficient and Receiver operating characteristic curve(ROC)was used to analyze the value of inflammatory cytokines in serum and cerebrospinal fluid for predicting the prognosis in patients with intracerebral hemorrhage.Results Compared with the control group,TNF-α,IL-6 and IL-8 levels in serum and cere-brospinal fluid were significantly increased in the intracerebral hemorrhage(P<0.001).The levels of TNF-α,IL-6 and IL-8 in serum and cerebrospinal fluid were higher in the severe intracerebral hemorrhage group than those in the mild-moderate group(P<0.01),and all of them were negatively correlated with the GCS score(r=-0.397,P<0.05;r=-0.587,P<0.01;r=-0.615,P<0.01;r=-0.696,P<0.01;r=-0.671,P<0.01;r=-0.510,P<0.01).Compared with patients in the group of hemor-rhage volume<30mL,TNF-α,IL-6 and IL-8 levels in cerebrospinal fluid of patients in the≥30 mL group were elevated(P<0.05),and in serum only IL-6 levels were elevated(P<0.05).The levels of TNF-α,IL-6 and IL-8 in serum and cerebrospinal fluid were elevated in the poor prognosis group compared with the good prognosis group(P<0.01).The area under the curve(AUC)of single and combined detection of TNF-α,IL-6 and IL-8 in the cerebrospinal fluid of patients with cerebral hemor-rhage for the first time on admission to the hospital for predicting the prognosis of patients with cerebral hemorrhage were 0.836,0.773,0.849,and 0.917,respectively.The AUC of single and combined tests of serum TNF-α,IL-6 and IL-8 in pa-tients within 24 h admission for predicting the prognosis were 0.692,0.808,0.721 and 0.843,respectively.Conclusions TNF-α,IL-6 and IL-8 levels are elevated in the cerebrospinal fluid of patients with intracerebral hemorrhage,and they cor-related with the severity of the patient′s condition.In addition,the levels of these indicators in the cerebrospinal fluid de-tected for the first time on admission may be used to predict the prognosis 90 days after discharge.