Laboratory of Human Nutrition, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.
Fernfachhochschule Schweiz, Brig, Switzerland.
Blood. 2021 Oct 14;138(15):1293-1303. doi: 10.1182/blood.2020010562.
Anemia of inflammation is a hallmark of tuberculosis. Factors controlling iron metabolism during anemia of inflammation and its resolution are uncertain. Whether iron supplements should be given during antituberculosis treatment to support hemoglobin (Hb) recovery is unclear. Before and during treatment of tuberculosis, we assessed iron kinetics, as well as changes in inflammation and iron metabolism indices. In a 26-week prospective study, Tanzanian adults with tuberculosis (N = 18) were studied before treatment and then every 2 weeks during treatment; oral and intravenous iron tracers were administered before treatment and after intensive phase (8/12 weeks) and complete treatment (24 weeks). No iron supplements were given. Before treatment, hepcidin and erythroferrone (ERFE) were greatly elevated, erythrocyte iron utilization was high (∼80%), and iron absorption was negligible (<1%). During treatment, hepcidin and interleukin-6 levels decreased ∼70% after only 2 weeks (P< .001); in contrast, ERFE did not significantly decrease until 8 weeks (P< .05). ERFE and interleukin-6 were the main opposing determinants of hepcidin (P< .05), and greater ERFE was associated with reticulocytosis and Hb repletion (P< .01). Dilution of baseline tracer concentration was 2.6-fold higher during intensive phase treatment (P< .01), indicating enhanced erythropoiesis. After treatment completion, iron absorption increased ∼20-fold (P< .001), and Hb increased ∼25% (P< .001). In tuberculosis-associated anemia of inflammation, our findings suggest that elevated ERFE is unable to suppress hepcidin, and iron absorption is negligible. During treatment, as inflammation resolves, ERFE may remain elevated, contributing to hepcidin suppression and Hb repletion. Iron is well absorbed only after tuberculosis treatment, and supplementation should be reserved for patients remaining anemic after treatment. This trial was registered at www.clinicaltrials.gov as #NCT02176772.
炎症性贫血是结核病的一个标志。控制炎症性贫血期间铁代谢及其恢复的因素尚不确定。在抗结核治疗期间是否应该给予铁补充剂以支持血红蛋白（Hb）恢复尚不清楚。在结核病治疗之前和期间，我们评估了铁动力学以及炎症和铁代谢指标的变化。在一项为期 26 周的前瞻性研究中，我们对坦桑尼亚成年人结核病（N = 18）进行了研究，在治疗前进行了研究，然后在治疗期间每 2 周进行一次研究；在治疗前和强化期（8/12 周）和完全治疗（24 周）后给予口服和静脉铁示踪剂。未给予铁补充剂。治疗前，铁调素和红细胞生成素（ERFE）大大升高，红细胞铁利用率高（约 80％），铁吸收可忽略不计（<1％）。在治疗过程中，仅在 2 周后，铁调素和白细胞介素-6 水平下降了约 70％（P<.001）；相比之下，直到 8 周时 ERFE 才明显下降（P<.05）。ERFE 和白细胞介素-6是铁调素的主要相反决定因素（P<.05），ERFE 较高与网织红细胞增多和 Hb 补充有关（P<.01）。在强化期治疗期间，基线示踪剂浓度的稀释率增加了 2.6 倍（P<.01），表明红细胞生成增强。治疗完成后，铁吸收增加了约 20 倍（P<.001），Hb 增加了约 25％（P<.001）。在与结核病相关的炎症性贫血中，我们的研究结果表明，升高的 ERFE 无法抑制铁调素，而铁吸收可忽略不计。在治疗过程中，随着炎症的消退，ERFE 可能仍然升高，从而有助于抑制铁调素和 Hb 补充。仅在结核病治疗后，铁才能很好地吸收，并且应保留给治疗后仍贫血的患者。该试验在 www.clinicaltrials.gov 上注册为 #NCT02176772。
