多发性骨髓瘤患者外周血单核细胞hepcidin与慢性病贫血相关

Peripheral Blood Monocyte Hepcidin in Patients with Multiple Myeloma is Associated with Anemia of Chronic Disease

Hepcidin异常升高引起铁利用障碍是导致慢性病贫血的主要机制。近年来发现单核细胞也可产生hepcidin,引起铁代谢异常。骨髓瘤患者血清和尿中hepcidin均升高,可能是导致慢性病贫血的病因之一,然而外周血单核细胞hepcidin是否也参与了慢性病贫血的发病,在目前尚不清楚。本研究探讨多发性骨髓瘤患者外周血单核细胞hepcidin在慢性病贫血发生机制中的作用。收集多发性骨髓瘤患者及健康志愿者的临床资料及外周静脉血,采用常规临床检验自动化方法检测基础实验室指标(如血红蛋白,血清铁蛋白等),采用ELISA法测定血清IL-6和TNF-α浓度,采用密度梯度离心法分离外周血单个核细胞,用CD14+磁珠从外周血单个核细胞中分选单核细胞,用Real time PCR测定外周血单核细胞Hepcidin,IL-6和TNF-αmRNA。结果表明,多发性骨髓瘤患者外周血单核细胞hepcidin表达高于正常对照,且与血红蛋白浓度呈负相关,在初治患者中hepcidin表达水平与铁蛋白和血清IL-6浓度正相关,与TNF-α无关。结论:多发性骨髓瘤患者外周血单核细胞hepcidin表达升高,可能参与慢性病贫血的发生。

Disorders of iron utilization caused by abnormal elevation of hepcidin levels are the main mechanism of anemia of chronic disease. Hepcidin is mainly produced by the liver. Recently it has boen found that monocytes are another source of hepcidin. The increased hepcidin in serum and urine of multiple myloma patients may be one cause of anemia of chronic disease （ACD）. However it is unclear whether the peripheral blood monocyte hepcidin is involved in the pathogenesis of anemia of chronic disease. This study was purposed to investigate the role of monocyte hepcidin in multiple myeloma patients with anemia of chronic disease. The clinical data and peripheral venous blood of multiple myeloma patients were collected. Serum concentration of IL-6 and TNF-α was detected by ELISA. Peripheral blood monocytes were isolated by CD14＋ magnetic beads. Hepcidin, IL-6 and TNF-α mRNA of monocytes were detected by real time quanta＇tative PCR. The results showed that the expression level of monocyte hepcidin mRNA in myeloma patients was higher than that in normal controls. In untreated patients, the expression level of monocyte hepcidin mRNA was negatively correlated with hemoglobin, and positively correlated with serum ferritin and IL-6 levels, but unrelated with TNF-α levels. It is concluded that the increased monocyte hepcidin levels in multiple myeloma patients may play an etiologic role in ACD.