脓毒症中炎症驱动的免疫重编程：从细胞因子风暴到免疫麻痹
Inflammation-driven immune reprogramming in sepsis: from cytokine storm to immunoparalysis.
摘要(中文译文)
脓毒症仍然是可预防性死亡的主要原因之一，部分原因在于其快速演变且高度异质的生物学特征在治疗开发和临床试验中常被当作统一的炎症综合征来处理。本叙述性综述综合了人体免疫谱分析的最新进展，将脓毒症重新定义为一种由炎症驱动的免疫重编程障碍，其特征为时间分辨的轨迹和生物学定义的亚型，其中高炎症反应与低反应程序可同时出现并在不同隔室间转换。我们总结了将早期先天感知、内皮损伤、凝血-炎症耦联及细胞因子网络“指令”与后期免疫麻痹、淋巴细胞丢失、功能性耗竭及慢性危重症表型相关联的核心机制。随后，我们将这些概念转化为动态免疫监测的实用解释框架，强调趋势和复合信号而非单一生物标志物，并强调患者状态、治疗方向与时机之间的错配如何有助于解释既往试验的失败。最后，我们概述了对下一代干预措施和研究设计的启示，主张在重复表型分析、富集入组以及捕捉继发感染、器官恢复轨迹和长期功能结局的终点指标指导下，进行双向、带时间戳的免疫调节。
Abstract
Sepsis remains a leading cause of preventable death, partly because its rapidly evolving and heterogeneous biology has often been treated as a uniform inflammatory syndrome in therapeutic development and clinical trials. This narrative review synthesizes recent advances in human immune profiling to reframe sepsis as an inflammation-driven immune reprogramming disorder characterized by time-resolved trajectories and biologically defined subtypes, in which hyperinflammation and low-response programs can arise in parallel and shift across compartments. We summarize core mechanisms linking early innate sensing, endothelial injury, coagulation-inflammation coupling, and cytokine network "instruction" to later immune paralysis, lymphocyte loss, functional exhaustion, and the chronic critical illness phenotype. We then translate these concepts into a practical interpretive framework for dynamic immune monitoring, emphasizing trends and composite signals over single biomarkers, and highlighting how misalignment of patient state, therapeutic direction, and timing helps explain past trial failures. Finally, we outline implications for next-generation interventions and study designs, arguing for bidirectional, time-stamped immunomodulation guided by repeated phenotyping, enriched enrollment, and endpoints that capture secondary infections, organ recovery trajectories, and longer-term functional outcomes.
如何引用
AMA
Sha Zhu, Ji He. Inflammation-driven immune reprogramming in sepsis: from cytokine storm to immunoparalysis.. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1887033.
APA
Sha Zhu, Ji He (2026). Inflammation-driven immune reprogramming in sepsis: from cytokine storm to immunoparalysis.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1887033
GB/T 7714
Sha Zhu, Ji He. Inflammation-driven immune reprogramming in sepsis: from cytokine storm to immunoparalysis.[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1887033.
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