Department of Pediatric Hematology-Oncology, Children's and Cancer Blood Foundation Laboratories, Weill Cornell Medical College, New York, NY;
Blood. 2014 Feb 20;123(8):1137-45. doi: 10.1182/blood-2013-08-521625. Epub 2013 Dec 19.
Anemia of inflammation (AI) is commonly observed in chronic inflammatory states and may hinder patient recovery and survival. Induction of hepcidin, mediated by interleukin 6, leads to iron-restricted erythropoiesis and anemia. Several translational studies have been directed at neutralizing hepcidin overexpression as a therapeutic strategy against AI. However, additional hepcidin-independent mechanisms contribute to AI, which are likely mediated by a direct effect of inflammatory cytokines on erythropoiesis. In this study, we used wild-type, hepcidin knockout (Hamp-KO) and interleukin 6 knockout (IL-6-KO) mice as models of AI. AI was induced with heat-killed Brucella abortus (BA). The distinct roles of iron metabolism and inflammation triggered by interleukin 6 and hepcidin were investigated. BA-treated wild-type mice showed increased expression of hepcidin and inflammatory cytokines, as well as transitory suppression of erythropoiesis and shortened red blood cell lifespan, all of which contributed to the severe anemia of these mice. In contrast, BA-treated Hamp-KO or IL-6-KO mice showed milder anemia and faster recovery compared with normal mice. Moreover, they exhibited different patterns in the development and resolution of anemia, supporting the notion that interleukin 6 and hepcidin play distinct roles in modulating erythropoiesis in AI.
炎症性贫血（AI）在慢性炎症状态中很常见，可能会阻碍患者的康复和生存。白细胞介素 6 介导的铁调素诱导导致铁限制的红细胞生成和贫血。已经有几项转化研究针对铁调素过表达作为治疗 AI 的策略。然而，AI 还存在其他铁调素非依赖性机制，可能是由炎症细胞因子对红细胞生成的直接作用介导的。在这项研究中，我们使用野生型、铁调素敲除（Hamp-KO）和白细胞介素 6 敲除（IL-6-KO）小鼠作为 AI 模型。用热灭活布鲁氏菌（BA）诱导 AI。研究了铁代谢和炎症引起的白细胞介素 6 和铁调素的不同作用。BA 处理的野生型小鼠表现出铁调素和炎症细胞因子表达增加，以及短暂的红细胞生成抑制和红细胞寿命缩短，所有这些都导致了这些小鼠的严重贫血。相比之下，BA 处理的 Hamp-KO 或 IL-6-KO 小鼠与正常小鼠相比，贫血程度较轻，恢复较快。此外，它们在贫血的发展和缓解中表现出不同的模式，支持白细胞介素 6 和铁调素在调节 AI 中的红细胞生成中发挥不同作用的观点。
