白介素-6在溶血性贫血中的作用：从炎症通路到治疗靶点
Interleukin-6 in hemolytic anemias: from inflammatory pathways to therapeutic targeting.
摘要(中文译文)
溶血性贫血包括以红细胞过早破坏为特征的遗传性和获得性疾病。越来越多的证据表明，多种形式的溶血均伴随持续性的炎症和免疫激活。红细胞破坏释放损伤相关分子模式，包括游离血红素和血红蛋白，可激活先天免疫通路、内皮细胞和凝血级联反应。白细胞介素-6（IL-6）是将溶血与全身性炎症、铁限制和自身免疫联系起来的核心介质。在本综述中，我们采用一个启发性的双轴框架，其中溶血诱导的IL-6促进铁调素依赖性铁隔离和急性期反应，同时还支持Tfh和Th17反应，损害调节性T细胞功能，并维持自身反应性或同种反应性B细胞。该框架的概念性推进不在于将IL-6视为一种统一的致病机制，而在于根据主要启动生物学和证据水平，将IL-6在不同溶血性疾病中置于不同位置。这些通路可能加重贫血、血栓形成和器官损伤。我们总结了IL-6参与自身免疫性溶血性贫血、Castleman病相关血细胞减少、镰状细胞病、地中海贫血、阵发性睡眠性血红蛋白尿、先天性红细胞膜和酶缺陷以及高溶血综合征的证据。我们还讨论了靶向IL-6、IL-6受体、JAK/STAT信号传导和IL-6反式信号传导的治疗策略。目前的临床证据仍然有限，但IL-6靶向治疗可能在部分难治性免疫介导性或巨噬细胞活化相关的溶血性疾病中具有合理性。未来的研究应优先关注基于机制的生物标志物以及前瞻性、生物标志物分层试验。
Abstract
Hemolytic anemias comprise inherited and acquired disorders characterized by premature red blood cell destruction. Increasing evidence indicates that many forms of hemolysis are accompanied by sustained inflammatory and immune activation. Red blood cell breakdown releases damage-associated molecular patterns, including free heme and hemoglobin, which activate innate immune pathways, endothelial cells and coagulation cascades. Interleukin-6 (IL-6) is a central mediator linking hemolysis to systemic inflammation, iron restriction and autoimmunity. In this review, we use a heuristic dual-axis framework in which hemolysis-induced IL-6 promotes hepcidin-dependent iron sequestration and acute-phase responses, while also supporting Tfh and Th17 responses, impairing regulatory T-cell function and sustaining autoreactive or alloreactive B cells. The conceptual advance of this framework is not to propose IL-6 as a uniform pathogenic mechanism, but to position IL-6 differently across hemolytic disorders according to the dominant initiating biology and level of evidence. These pathways may aggravate anemia, thrombosis and organ injury. We summarize evidence for IL-6 involvement in autoimmune hemolytic anemia, Castleman disease-associated cytopenias, sickle cell disease, thalassemia, paroxysmal nocturnal hemoglobinuria, congenital red-cell membrane and enzyme defects, and hyperhemolysis syndrome. We also discuss therapeutic strategies targeting IL-6, IL-6 receptor, JAK/STAT signaling and IL-6 trans-signaling. Current clinical evidence remains limited, but IL-6-directed therapy may be rational in selected refractory immune-mediated or macrophage-activation-associated hemolytic disorders. Future studies should prioritize mechanism-based biomarkers and prospective, biomarker-stratified trials.
如何引用
AMA
Manjun Zhao, Xin Yu. Interleukin-6 in hemolytic anemias: from inflammatory pathways to therapeutic targeting.. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1919619.
APA
Manjun Zhao, Xin Yu (2026). Interleukin-6 in hemolytic anemias: from inflammatory pathways to therapeutic targeting.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1919619
GB/T 7714
Manjun Zhao, Xin Yu. Interleukin-6 in hemolytic anemias: from inflammatory pathways to therapeutic targeting.[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1919619.
在 PubMed增强版 阅读全文
翻译全文 · AI 文献问答 · PDF 原文下载 · 引用导出