Department of Pediatrics, Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc, I. P. Pavlova 185/6, Olomouc, 779 00, Czech Republic.
Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc, Olomouc, Czech Republic.
Dig Dis Sci. 2021 Oct;66(10):3263-3269. doi: 10.1007/s10620-020-06652-1. Epub 2020 Oct 16.
Anemia is the most common extraintestinal systemic complication of inflammatory bowel disease. Iron deficiency anemia and anemia of chronic disease are among the most frequent types. Intestinal iron absorption is controlled by the activity of ferroportin. Cells with high expression of ferroportin include enterocytes, and also macrophages and hepatocytes. Iron homeostasis is controlled by the hepcidin-ferroportin axis. Hepcidin is a central regulator of iron metabolism and can also serve as a marker of systemic inflammation. During systemic inflammatory response, the synthesis of hepcidin increases, and hepcidin binds to ferroportin and inhibits its activity. Thus, iron is not absorbed from the bowel into the circulation and also remains sequestered in macrophages. Conversely, hepcidin synthesis is suppressed during conditions requiring increased iron intake for enhanced erythropoiesis, such as iron deficiency anemia or hypoxia. Here, ferroportin is not blocked, and iron is actively absorbed into the bloodstream and also released from the stores. Production of hepcidin is influenced by the status of total body iron stores, systemic inflammatory activity and erythropoietic activity. Oral iron therapy is limited in inflammatory bowel diseases due to ongoing gastrointestinal inflammation. It is less effective and may worsen the underlying disease. Therefore, the choice between oral and parenteral iron therapy must be made with caution. Oral iron would be ineffective at high hepcidin levels due to concurrent ferroportin blockage. Contrarily, low levels of hepcidin indicate that oral iron therapy should be successful. An understanding of hepcidin can help in understanding the body's reaction to iron depletion during the inflammatory process.
贫血是炎症性肠病最常见的肠道外全身并发症。缺铁性贫血和慢性病贫血是最常见的类型之一。肠道铁吸收受铁蛋白的活性控制。铁蛋白高表达的细胞包括肠细胞,还有巨噬细胞和肝细胞。铁稳态由hepcidin-ferroportin 轴控制。hepcidin 是铁代谢的中枢调节剂,也可以作为全身炎症的标志物。在全身炎症反应中,hepcidin 的合成增加,hepcidin 与 ferroportin 结合并抑制其活性。因此,铁不能从肠道吸收到循环中,也仍然滞留在巨噬细胞中。相反,在需要增加铁摄入以增强红细胞生成的情况下,如缺铁性贫血或缺氧,hepcidin 的合成受到抑制。此时, ferroportin 不受抑制,铁被主动吸收到血液中,并从储存中释放出来。hepcidin 的产生受全身铁储存状态、全身炎症活动和红细胞生成活性的影响。由于持续的胃肠道炎症,口服铁剂在炎症性肠病中的应用受到限制。它的效果较差,并且可能使基础疾病恶化。因此,必须谨慎选择口服和肠外铁剂治疗。由于铁蛋白的同时阻断,高 hepcidin 水平时口服铁剂无效。相反,hepcidin 水平低表明口服铁剂治疗应该有效。了解 hepcidin 有助于理解在炎症过程中机体对铁耗竭的反应。