Haematologica. 2013 Oct;98(10):1633-40. doi: 10.3324/haematol.2013.087114. Epub 2013 Aug 30.
Anemia is common in older adults and associated with adverse health outcomes in epidemiological studies. A thorough understanding of the complex pathophysiological mechanisms driving anemia in the elderly is lacking; but inflammation, iron restriction, and impaired erythroid maturation are thought to influence the phenotype. We hypothesized that interleukin-6 contributes to this anemia, given its pro-inflammatory activities, its ability to induce hepcidin antimicrobial peptide, and its negative impact on several tissues in older adults. We tested this hypothesis by comparing changes in indices of inflammation, iron metabolism and erythropoiesis in aged C57BL/6 mice to aged mice with targeted deletions of interleukin-6 or hepcidin antimicrobial peptide. Circulating neutrophil and monocyte numbers and inflammatory cytokines increased with age. Decline in hemoglobin concentration and red blood cell number indicated that C57BL/6, interleukin-6 knockout mice, and hepcidin antimicrobial peptide knockout mice all demonstrated impaired erythropoiesis by 24 months. However, the interleukin-6 knock out genotype and the hepcidin antimicrobial peptide knock out genotype resulted in improved erythropoiesis in aged mice. Increased erythropoietic activity in the spleen suggested that the erythroid compartment was stressed in aged C57BL/6 mice compared to aged interleukin-6 knockout mice. Our data suggest C57BL/6 mice are an appropriate mammalian model for the study of anemia with age. Furthermore, although interleukin-6 and hepcidin antimicrobial peptide are not required, they can participate in the development of anemia in aging mice, and could be targeted, pre-clinically, with existing interventions to determine the feasibility of such agents for the treatment of anemia in older adults.
老年人贫血很常见，且与流行病学研究中的不良健康结果相关。人们对导致老年人贫血的复杂病理生理机制缺乏深入了解；但炎症、铁限制和红细胞生成受损被认为会影响其表型。鉴于白细胞介素 6 的促炎活性、诱导抗菌肽 hepcidin 的能力及其对老年人多个组织的负面影响，我们假设白细胞介素 6 会导致这种贫血。我们通过比较年龄增长时炎症、铁代谢和红细胞生成的指数变化，来检验这一假说，比较对象是 C57BL/6 老年小鼠和靶向缺失白细胞介素 6 或抗菌肽 hepcidin 的老年小鼠。循环中性粒细胞和单核细胞数量以及炎症细胞因子随年龄增长而增加。血红蛋白浓度和红细胞数量下降表明，24 月龄时 C57BL/6 小鼠、白细胞介素 6 基因敲除小鼠和抗菌肽 hepcidin 基因敲除小鼠均出现红细胞生成受损。然而，白细胞介素 6 基因敲除和抗菌肽 hepcidin 基因敲除使老年小鼠的红细胞生成得到改善。脾脏中红细胞生成活性增加表明，与白细胞介素 6 基因敲除的老年小鼠相比，C57BL/6 老年小鼠的红细胞系受到了压力。我们的数据表明，C57BL/6 小鼠是研究与年龄相关贫血的合适哺乳动物模型。此外，尽管白细胞介素 6 和抗菌肽 hepcidin 并非必需，但它们可能参与了衰老小鼠贫血的发生，并且可以用现有的干预措施来靶向它们，以确定这些药物在治疗老年人贫血方面的可行性。
