High-dose parenteral iron sucrose depresses neutrophil intracellular killing capacity
High-dose parenteral iron sucrose depresses neutrophil intracellular killing capacity
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DOI：
10.1046/j.1523-1755.2003.00125.x
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发表时间：
2003-08-01
影响因子：
19.6
通讯作者：
Hörl, WH
中科院分区：
文献类型：
--
作者：
Deicher, R;Ziai, F;Hörl, WH
背景铁对血红蛋白的形成至关重要。在用人重组促红细胞生成素（rhEPO）的长期治疗期间，大多数终末期肾病（ESRD）患者对rhEPO没有充分反应，除非用静脉内铁替代。然而，存在的关注可能的有害影响，胃肠外铁对细胞宿主防御和铁介导的氧化应激的增量。我们分析了20例终末期肾病患者腹膜透析中分离的多形核白细胞（PMN）的吞噬功能，以随机、双盲的方式静脉注射300 mg蔗糖铁或安慰剂2小时以上。我们在给药前、给药期间、给药后1小时和给药后2天评估了Fc γ R依赖的吞噬作用和对调理大肠杆菌的杀伤作用（主要结果变量）、Fc γ R依赖的氧化爆发能力和补体受体3（CR 3、Mac 1、CD 11b/CD 18）/肿瘤坏死因子α（TNF α）介导的杀菌乳铁蛋白释放。E.与安慰剂治疗组相比，经蔗糖铁治疗的腹膜透析患者的PMN杀死的大肠杆菌随着时间的推移显著降低（分别为F = 3.48，df = 4，P = 0.008; F = 3.99，df = 4，P = 0.006）。所有次要结果变量在两组间无差异。从ESRD患者中分离的PMN的杀伤能力在对高剂量肠外蔗糖铁的反应中降低，这可能部分解释了接受频繁和高剂量肠外铁的透析患者的住院率较高和生存率较低的报道。
Background. Iron is essential for the formation of hemoglobin. During long-term treatment with human recombinant erythropoietin (rhEPO), the majority of end-stage renal disease (ESRD) patients will not respond adequately to rhEPO unless substituted with intravenous iron. However, concern exists about possible detrimental effects of parenteral iron on cellular host defense and iron-mediated increments of oxidative stress.Methods. We analyzed phagocytic functions of polymorphonuclear leukocytes (PMN) isolated from 20 ESRD patients on peritoneal dialysis in response to 300 mg of iron sucrose or placebo administered intravenously over two hours in a randomized, double-blind manner. We evaluated FcgammaR-dependent phagocytosis and killing (primary outcome variable) of opsonized Escherichia coli , FcgammaR-dependent oxidative burst capacity, and complement receptor 3 (CR3, Mac1, CD11b/CD18)/tumor necrosis factor alpha (TNFalpha)-mediated release of bactericidal lactoferrin before, during, one hour, and two days after administration.Results. The absolute count and the percentage of E. coli killed by PMN of iron sucrose-treated peritoneal dialysis patients decreased significantly over time in comparison to placebo-treated patients (F = 3.48, df = 4, P = 0.008; F = 3.99, df = 4, P = 0.006, respectively). All secondary outcome variables were not different between both groups over time.Conclusions. Killing capacity of PMN isolated from ESRD patients decreases in response to high-dose parenteral iron sucrose, possibly in part explaining reported higher hospitalization rates and lower survival rates of dialysis patients receiving frequent and high-dose parenteral iron.