Background Febrile neutropenia is a common and serious complication during treatment of childhood cancer. Empirical broad-spectrum antibiotics are usually administered until neutrophil cell count recovery. It was the aim of this study to investigate cytokine profiles as potential biomarkers using in-vitro sepsis models to differentiate between distinct clinical courses of febrile neutropenia (FN). Methods We conducted an observational study in FN episodes of pediatric oncology patients. Courses of neutropenia were defined as severe in case of proven blood stream infection or clinical evidence of complicated infection. We collected blood samples at various time points from the onset of FN and stimulated ex vivo with lipopolysaccharide (LPS) and Staphylococcus epidermidis (SE) for 24 h. Twenty-seven cytokine levels were measured in the whole blood culture supernatants by a multiplex immunoassay system. Results Forty-seven FN episodes from 33 children were investigated. IL-8, IL-1β, and MCP-1 expression increased significantly over time. IL-8, MIP-1α, MIP-1β, MCP-1, and TNF-α showed significantly lower concentration in patients with a clinically severe course of the FN. Conclusions Distinct patterns of cytokine profiles seem to be able to determine infectious FN and to predict the severity of its clinical course. If these data can be verified in a multi-centre setting, this may finally lead to an individualized treatment strategy facilitating antibiotic stewardship in these patients.

中文翻译：

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促炎细胞因子比率决定接受化疗的儿童发热性中性粒细胞减少症的临床病程

背景 发热性中性粒细胞减少症是儿童癌症治疗期间常见且严重的并发症。通常给予经验性广谱抗生素直至中性粒细胞计数恢复。本研究的目的是使用体外脓毒症模型来研究细胞因子谱作为潜在生物标志物，以区分发热性中性粒细胞减少症 (FN) 的不同临床病程。方法 我们对儿科肿瘤患者的 FN 发作进行了观察性研究。在经证实的血流感染或复杂感染的临床证据的情况下，中性粒细胞减少的病程被定义为严重的。我们在 FN 发病后的不同时间点收集血液样本，并用脂多糖 (LPS) 和表皮葡萄球菌 (SE) 离体刺激 24 小时。通过多重免疫分析系统在全血培养上清液中测量了 27 种细胞因子水平。结果 调查了 33 名儿童的 47 次 FN 发作。IL-8、IL-1β 和 MCP-1 表达随时间显着增加。IL-8、MIP-1α、MIP-1β、MCP-1 和 TNF-α 在具有临床严重 FN 病程的患者中显示出显着较低的浓度。结论 细胞因子谱的不同模式似乎能够确定感染性 FN 并预测其临床病程的严重程度。如果这些数据可以在多中心环境中得到验证，这可能最终会导致个性化的治疗策略，促进对这些患者的抗生素管理。和 MCP-1 表达随时间显着增加。IL-8、MIP-1α、MIP-1β、MCP-1 和 TNF-α 在具有临床严重 FN 病程的患者中显示出显着较低的浓度。结论 细胞因子谱的不同模式似乎能够确定感染性 FN 并预测其临床病程的严重程度。如果这些数据可以在多中心环境中得到验证，这可能最终会导致个性化的治疗策略，促进对这些患者的抗生素管理。和 MCP-1 表达随时间显着增加。IL-8、MIP-1α、MIP-1β、MCP-1 和 TNF-α 在具有临床严重 FN 病程的患者中显示出显着较低的浓度。结论 细胞因子谱的不同模式似乎能够确定感染性 FN 并预测其临床病程的严重程度。如果这些数据可以在多中心环境中得到验证，这可能最终会导致个性化的治疗策略，促进对这些患者的抗生素管理。