Office of Research and Development, Department of Veterans Affairs, Washington, DC 20420, USA.
Department of Surgery, Uniformed University of the Health Sciences, Bethesda, MD 20814, USA.
Metallomics. 2021 Jun 11;13(6). doi: 10.1093/mtomcs/mfab030.
This report provides perspectives concerning dual roles of serum ferritin as a measure of both iron status and inflammation. We suggest benefits of a lower range of serum ferritin as has occurred for total serum cholesterol and fasting blood glucose levels. Observations during a prospective randomized study using phlebotomy in patients with peripheral arterial disease offered unique insights into dual roles of serum ferritin both as an iron status marker and acute phase reactant. Robust positive associations between serum ferritin, interleukin 6 [IL-6], tissue necrosis factor-alpha, and high sensitivity C-reactive protein were discovered. Elevated serum ferritin and IL-6 levels associated with increased mortality and with reduced mortality at ferritin levels <100 ng mL-1. Epidemiologic studies demonstrate similar outcomes. Extremely elevated ferritin and IL-6 levels also occur in individuals with high mortality due to SARS-CoV-2 infection. Disordered iron metabolism reflected by a high range of serum ferritin level signals disease severity and outcomes. Based upon experimental and epidemiologic data, we suggest testing the hypotheses that optimal ferritin levels for cardiovascular mortality reduction range from 20 to 100 ng mL-1 with % transferrin levels from 20 to 50%, to ensure adequate iron status and that ferritin levels above 194 ng mL-1 associate with all-cause mortality in population cohorts.
本报告提供了有关血清铁蛋白作为铁状态和炎症指标的双重作用的观点。我们建议将血清铁蛋白的范围降低到类似于总血清胆固醇和空腹血糖水平的范围，以获得益处。在一项使用静脉采血的前瞻性随机研究中，对周围动脉疾病患者的观察提供了对血清铁蛋白作为铁状态标志物和急性反应反应物的双重作用的独特见解。发现了血清铁蛋白、白细胞介素 6（IL-6）、肿瘤坏死因子-α和高敏 C 反应蛋白之间的强正相关关系。较高的血清铁蛋白和 IL-6 水平与死亡率增加有关，而在铁蛋白水平<100ng/mL-1时与死亡率降低有关。流行病学研究表明了类似的结果。在 SARS-CoV-2 感染导致高死亡率的个体中，也会出现极高的铁蛋白和 IL-6 水平。通过高血清铁蛋白水平反映的铁代谢紊乱表明疾病的严重程度和结果。基于实验和流行病学数据，我们建议检验以下假设：降低心血管死亡率的最佳铁蛋白水平范围为 20 至 100ng/mL-1，转铁蛋白水平范围为 20%至 50%，以确保充足的铁状态，并且铁蛋白水平高于 194ng/mL-1与人群队列中的全因死亡率相关。
