Regulation of iron homeostasis in anemia of chronic disease and iron deficiency anemia: diagnostic and therapeutic implications
Regulation of iron homeostasis in anemia of chronic disease and iron deficiency anemia: diagnostic and therapeutic implications
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DOI：
10.1182/blood-2008-12-195651
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发表时间：
2009-05-21
期刊：
影响因子：
20.3
通讯作者：
Weiss, Guenter
中科院分区：
文献类型：
--
作者：
Theurl, Igor;Aigner, Elmar;Weiss, Guenter
慢性病贫血（ACD）的特征是由细胞因子和主要调节因子铁调素诱导的巨噬细胞铁潴留。铁调素通过与铁输出蛋白ferroportin结合来控制细胞铁流出。然而，许多患者同时患有ACD和缺铁性贫血（ACD/IDA），后者是由慢性失血引起的。我们使用大鼠模型的ACD慢性关节炎和模仿ACD/IDA额外的放血定义不同的铁调节途径。炎症过程中的铁潴留发生在巨噬细胞和脾脏中，但不在肝脏中。在患有ACD的大鼠和人类中，血清铁调素浓度升高，这是由膜铁转运蛋白的十二指肠和巨噬细胞表达降低引起的。患有ACD/IDA的个体具有比ACD受试者显著更低的铁调素水平，并且与ACD受试者相反，ACD/IDA人能够从肠道吸收膳食铁并从巨噬细胞动员铁。循环铁调素水平影响ACD和ACD/IDA中的铁运输，并且对红细胞生成对铁的需求比对炎症更敏感。铁调素测定可能有助于区分ACD和ACD/IDA，并为这些患者选择适当的治疗方法。（血。2009; 113：5277-5286）
The anemia of chronic disease (ACD) is characterized by macrophage iron retention induced by cytokines and the master regulator hepcidin. Hepcidin controls cellular iron efflux on binding to the iron export protein ferroportin. Many patients, however, present with both ACD and iron deficiency anemia (ACD/IDA), the latter resulting from chronic blood loss. We used a rat model of ACD resulting from chronic arthritis and mimicked ACD/IDA by additional phlebotomy to define differing iron-regulatory pathways. Iron retention during inflammation occurs in macrophages and the spleen, but not in the liver. In rats and humans with ACD, serum hepcidin concentrations are elevated, which is paralleled by reduced duodenal and macrophage expression of ferroportin. Individuals with ACD/IDA have significantly lower hepcidin levels than ACD subjects, and ACD/IDA persons, in contrast to ACD subjects, were able to absorb dietary iron from the gut and to mobilize iron from macrophages. Circulating hepcidin levels affect iron traffic in ACD and ACD/IDA and are more responsive to the erythropoietic demands for iron than to inflammation. Hepcidin determination may aid to differentiate between ACD and ACD/IDA and in selecting appropriate therapy for these patients. (Blood. 2009; 113: 5277-5286)