Th1/Th2细胞因子对粒细胞缺乏和非粒细胞缺乏脓毒症患儿预后评估的意义

The prognostic value of Th1/Th2 cytokines on septic children with or without neutropenia

目的探讨粒细胞缺乏(粒缺)和非粒细胞缺乏(非粒缺)的脓毒症患儿细胞因子特点及与预后的关系。方法138例诊断为脓毒症的患儿,根据外周血中性粒细胞绝对计数,分为粒缺组、非粒缺组,根据有无脓毒性休克,分为休克组、非休克组,分别分析各组炎性指标(CRP、PCT)、Th1/Th2细胞因子(IL-2、IL-4、IL-6、IL-10、TNF-α、INF-γ)、PRISM-Ⅲ评分及治疗转归。结果1)138例脓毒症患儿,64例为粒缺,74例为非粒缺,粒缺组PRISM-Ⅲ评分显著高于非粒缺组(P=0.048),两组患儿的病死率差异无统计学意义(P=0.4),粒缺组住院时间显著延长(P=0.02)。粒缺组CRP、IL-6、IL-10显著高于非粒缺组(P=0.001;P=0.001;P=0.032),粒缺组TNF-α显著低于非粒缺组(P=0.032)。2)在64例粒缺脓毒症患儿中有23例为脓毒性休克,41例非脓毒性休克,休克组PRISM-Ⅲ显著高于非休克组(P=0.001),休克组病死率(10/23,43.5%)显著高于非休克组(1/41,2.4%)(P=0.001)。休克组的CRP、PCT、IL-6、IL-10、TNF-α显著高于非休克组(P=0.001;P=0.001;P=0.001;P=0.005;P=0.019),ROC曲线分析,IL-6曲线下面积为0.80,Cut-off值为315.38 pg/mL,IL-10曲线下面积为0.80,Cut-off值为45.18 pg/mL,TNF-α曲线下面积为0.85,Cut-off值为1.95 pg/mL。3)在74例非粒缺脓毒症患儿中,19例为脓毒性休克,55例非脓毒性休克,休克组PRISM-Ⅲ显著高于非休克组(P=0.022),两组病死率比较差异无统计学意义(P=0.3)。休克组IL-10显著高于非休克组(P=0.015)。4)对42例脓毒性休克的患儿分析,23例为粒缺组,19例为非粒缺组,粒缺组PRISM-Ⅲ评分显著高于非粒缺组(P=0.005),粒缺组病死率(47.8%)和非粒缺(31.6%)差异无统计学意义(P=0.29)。粒缺组CRP、PCT、IL-6、IL-10因子显著高于非粒缺组(P=0.001;P=0.001;P=0.001;P=0.035),两组TNF-α差异无统计学意义(P=0.57)。5)分析96例非脓毒性休克的患儿,41例为粒缺组,55例为非粒缺组,两组PRISM-Ⅲ评分差异无统计学意义(P=0.6),非粒缺组病死率(20%)显著高于粒缺组(2.4%)(P=0.02)。粒缺组CRP、IL-6显著高于非粒缺组(P=0.005;P=0.033),粒缺组TNF-α显著低于非粒缺组(P=0.007)。结论合并粒缺的脓毒症患儿病情严重,治疗时间长。粒缺患儿发展为脓毒性休克时病死率显著增高,其IL-6、IL-10、TNF-α也显著升高。IL-6、IL-10、TNF-α可以帮助预测脓毒症患儿的预后。

Objective To explore the characteristics and value for predicting prognosis of cytokines in septic children with or without neutropenia. Methods Totally 138 septic children were divided into the neutropenia and non-neutropenia groups according to absolute neutropenic count. Septic children were divided into the shock and non-shock groups according to circulation function and organ perfusion. The levels of C-reactive protein, procalcitonin, cytokines, PRISM-Ⅲ and clinical outcomes were analyzed between the relative groups. Results(1) Totally 138 septic children were recruited, 64 with neutropenia and 74 without neutropenia. The level of PRISM-Ⅲ of the neutropenia group was significantly higher than that of the non-neutropenia group (P=0.048).Mortality showed no significant difference between the two groups, but hospital stay in the neutropenia group was longer than that in the non-neutropenia group. The levels of C-reactive protein, IL-6, and IL-10 ihe neutropenia group were significantly higher than those of the non-neutropenia group (P=0.001;P=0.001;P=0.032). The level of TNF-α in the neutropenia group was significantly lower than that of the non-neutropenia group (P=0.032).(2)Among the 64 septic children with neutropenia, 23 were combined with shock. The PRISM-Ⅲ level of the shock group was significantly higher than that of the non-shock group (P=0.001). The mortality of the shock group (43.5%, 10/23) was significantly higher than the non-shock group (2.4%, 1/41)(P=0.001). C-reactive protein, procalcitonin, IL-6, IL-10 and TNF-α in the shock group elevated obviously than those in the non-shock group (P=0.001;P=0.001;P=0.001;P=0.005;P=0.019). The area under receiver operating characteristic curve was 0.8 for IL-6 (cut-off value 315.38 pg/mL), 0.8 for IL-10 (cut-off value 45.18 pg/mL), and 0.85 for TNF-α(cut-off value 1.95 pg/mL).(3) Among the 74 septic children without neutropenia, 19 were combined with shock. The PRISM-Ⅲ level of the shock group was significantly higher than that of the non-shock group (P=0.022).There was no significant difference of mortality between the two groups (P=0.3). IL-10 level in the shock group elevated obviously than that in the non-shock group (P=0.015).(4) Among the 42 children with sepsis shock, 23 were combined with neutropenia. The PRISM-Ⅲ level of the neutropenia group was significantly higher than that of the non-neutropenia group (P=0.005). There was no significant difference of mortality between the two groups (P=0.29). The levels of C-reactive protein, procalcitonin, IL-6 and IL-10 in the neutropenia group were significantly higher than those in the non-neutropenia group (P=0.001;P=0.001;P=0.001;P=0.035). There was no difference of TNF-α level between the two groups.(5) Among the 96 children without sepsis shock, 41 were combined with neutropenia. No difference of PRISM-Ⅲ level was observed between the neutropenia and non-neutropenia groups. The mortality of the neutropenia group was significantly lower than that in the non-neutropenia group (2.4% vs 20%, P=0.02). The levels of C-reactive protein and IL-6 in the neutropenia group were significantly higher than those in the non-neutropenia group (P=0.005;P=0.033). The TNF-α level was significantly lower than that in the non-neutropenia group (P=0.007). Conclusions Compared to children without neutropenia, septic children combined with neutropenia have longer hospital stay, and septic shock children combined with neutropenia have higher mortality, and levels of IL-6, IL-10 and TNF-α were also significantly increased. The levels of IL-6, IL-10 and TNF-α can help to predict prognosis of children with sepsis.