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采用流式细胞术微珠阵列技术评估 Th1/Th2 细胞因子作为儿科血液/肿瘤患者严重感染的快速诊断工具。

Evaluation of Th1/Th2 cytokines as a rapid diagnostic tool for severe infection in paediatric haematology/oncology patients by the use of cytometric bead array technology.

机构信息

Division of Haematology-Oncology, Zhejiang Key Laboratory for Neonatal Diseases, the Children's Hospital of Zhejiang University School of Medicine, Hangzhou, China.

出版信息

Clin Microbiol Infect. 2011 Nov;17(11):1666-73. doi: 10.1111/j.1469-0691.2011.03490.x. Epub 2011 Apr 4.

DOI:10.1111/j.1469-0691.2011.03490.x
PMID:21463393
Abstract

Haematology/oncology children are usually at risk for various infections after intensive chemotherapy. We evaluated the quantification of Th1/Th2 cytokines with a flow cytometric bead array (CBA) in 795 hospitalized haematology/oncology children (309 febrile and 486 afebrile patients) to seek for a diagnostic method for determination of the type and the severity of infection. Three hundred and nine febrile patients developed a total of 505 febrile episodes. Microbiological examination demonstrated a positive blood culture (microbiologically documented infection (MDI)) in 145/505 febrile episodes. The controls included 550 healthy children, 43 haemophagocytic lymphohistiocytosis (HLH) patients, 35 cytomegalovirus infection patients and 19 Epstein-Barr virus infection patients. Interleukin (IL)-4, IL-6, IL-10, tumour necrosis factor (TNF)-α and interferon (IFN)-γ levels in febrile episodes were significantly higher than those in healthy children, and the cytokine profile was different from that of the HLH controls or the viral infection controls. IL-6 levels were much higher in MDI patients (usually >1000.0 pg/mL, 60/145) than in HLH patients (2/43); however, IFN-γ levels were only slightly increased in MDI patients, rarely being more than 100.0 pg/mL (8/145 vs. 39/43 in HLH patients). The median levels of IL-4, IL-6, IL-10, TNF-α and IFN-γ in febrile patients before antibiotic therapy were 3.9, 660.1, 122.7, 6.9 and 11.4 pg/mL, respectively, and returned to 3.3, 22.8, 9.6, 4.1 and 6.4 pg/mL, respectively, after infection was controlled. IL-6 and IL-10 levels were positively associated with septic shock and mortality rates. In conclusion, our results have demonstrated the usefulness of IL-6/IL-10/TNF-α/IFN-γ determination with CBA technology for the early rapid diagnosis, severity evaluation and assessment of therapy effect in febrile haematology/oncology children.

摘要

血液肿瘤学儿童在接受强化化疗后通常存在各种感染的风险。我们使用流式细胞术微珠阵列(CBA)评估了 795 例住院血液肿瘤学儿童(309 例发热和 486 例不发热患者)中 Th1/Th2 细胞因子的定量,以寻找一种用于确定感染类型和严重程度的诊断方法。309 例发热患者共发生 505 次发热发作。微生物学检查显示,505 次发热发作中有 145 次(微生物学确诊感染(MDI))血培养阳性。对照组包括 550 名健康儿童、43 例噬血细胞性淋巴组织细胞增生症(HLH)患者、35 例巨细胞病毒感染患者和 19 例 EBV 感染患者。发热发作时白细胞介素(IL)-4、IL-6、IL-10、肿瘤坏死因子(TNF)-α和干扰素(IFN)-γ水平明显高于健康儿童,细胞因子谱与 HLH 对照组或病毒感染对照组不同。在 MDI 患者(通常 >1000.0 pg/mL,60/145)中,IL-6 水平明显高于 HLH 患者(2/43);然而,在 MDI 患者中 IFN-γ 水平仅略有升高,很少超过 100.0 pg/mL(8/145 比 HLH 患者中的 39/43)。抗生素治疗前发热患者的 IL-4、IL-6、IL-10、TNF-α和 IFN-γ中位水平分别为 3.9、660.1、122.7、6.9 和 11.4 pg/mL,感染得到控制后分别恢复至 3.3、22.8、9.6、4.1 和 6.4 pg/mL。IL-6 和 IL-10 水平与感染性休克和死亡率呈正相关。总之,我们的研究结果表明,CBA 技术检测 IL-6/IL-10/TNF-α/IFN-γ 对于发热血液肿瘤学儿童的早期快速诊断、严重程度评估和治疗效果评估具有一定的应用价值。

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