Distinct roles for hepcidin and interleukin-6 in the recovery from anemia in mice injected with heat-killed Brucella abortus
Distinct roles for hepcidin and interleukin-6 in the recovery from anemia in mice injected with heat-killed Brucella abortus
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DOI：
10.1182/blood-2013-08-521625
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发表时间：
2014-02-20
期刊：
影响因子：
20.3
通讯作者：
Rivella, Stefano
中科院分区：
文献类型：
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作者：
Gardenghi, Sara;Renaud, Tom M.;Rivella, Stefano
炎症性贫血（AI）通常在慢性炎症状态下观察到，并可能阻碍患者的恢复和生存。由白细胞介素6介导的铁调素的诱导导致铁限制性红细胞生成和贫血。一些翻译研究已经针对中和铁调素过表达作为针对AI的治疗策略。然而，另外的铁调素非依赖性机制有助于AI，这可能是由炎性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。用热灭活的牛种布鲁氏菌（BA）诱导AI。研究了白细胞介素6和铁调素在铁代谢和炎症中的不同作用。BA处理的野生型小鼠显示铁调素和炎性细胞因子的表达增加，以及红细胞生成的暂时抑制和红细胞寿命缩短，所有这些都导致这些小鼠的严重贫血。与此相反，BA治疗的Hamp-KO或IL-6-KO小鼠表现出较轻的贫血和更快的恢复与正常小鼠相比。此外，它们在贫血的发展和消退中表现出不同的模式，支持白细胞介素6和铁调素在AI中调节红细胞生成中发挥不同作用的观点。
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.