Anemia is a major health issue and associated with increased morbidity. Iron deficiency anemia (IDA) is the most prevalent, followed by anemia of chronic disease (ACD). IDA and ACD often coexist, challenging diagnosis and treatment. While iron supplementation is the first-line therapy for IDA, its optimal route of administration and the efficacy of different repletion strategies in ACD are elusive. Female Lewis rats were injected with group A streptococcal peptidoglycan-polysaccharide (PG-APS) to induce inflammatory arthritis with associated ACD and/or repeatedly phlebotomized and fed with low iron diet to induce IDA, or a combination thereof (ACD/IDA). Iron was either supplemented by daily oral gavage of Ferric Maltol or by weekly intravenous (i.v.) injection of Ferric Carboxymaltose for up to four weeks. While both strategies reversed IDA, they remained ineffective to improve hemoglobin (Hb) levels in ACD, although oral iron showed slight amelioration of various erythropoiesis-associated parameters. In contrast, both iron treatments significantly increased Hb in ACD/IDA. In ACD and ACD/IDA animals, i.v. iron administration resulted in iron trapping in liver and splenic macrophages, induction of ferritin expression and increased circulating levels of the iron hormone hepcidin and the inflammatory cytokine interleukin-6 (IL-6), while oral iron supplementation reduced IL-6 levels. Thus, oral and i.v. iron resulted in divergent effects on systemic and tissue iron homeostasis and inflammation. Our results indicate that both iron supplements improve Hb in ACD/IDA, but are ineffective in ACD with pronounced inflammation, and that under the latter condition, i.v. iron is trapped in macrophages and may enhance inflammation.

中文翻译：

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口服和静脉铁剂治疗炎症性贫血和缺铁大鼠模型的比较分析。

贫血是一个主要的健康问题，与发病率增加有关。缺铁性贫血（IDA）最为常见，其次是慢性病贫血（ACD）。IDA 和 ACD 经常共存，给诊断和治疗带来挑战。虽然补铁是 IDA 的一线治疗方法，但其最佳给药途径以及不同补铁策略在 ACD 中的疗效尚不清楚。给雌性Lewis大鼠注射A组链球菌肽聚糖-多糖（PG-APS）以诱导伴有ACD的炎性关节炎和/或反复静脉切开并喂食低铁饮食以诱导IDA，或其组合（ACD/IDA）。通过每天口服麦芽酚铁或每周静脉注射羧基麦芽糖铁来补充铁，持续长达四个星期。虽然这两种策略都逆转了 IDA，但它们对于改善 ACD 中的血红蛋白 (Hb) 水平仍然无效，尽管口服铁剂显示出各种红细胞生成相关参数的轻微改善。相比之下，两种铁治疗均显着增加了 ACD/IDA 中的 Hb。在 ACD 和 ACD/IDA 动物中，静脉注射铁剂导致铁被捕获在肝脏和脾脏巨噬细胞中，诱导铁蛋白表达并增加铁激素铁调素和炎症细胞因子白细胞介素 6 (IL-6) 的循环水平，而口服铁剂则补充可降低 IL-6 水平。因此，口服铁剂和静脉注射铁剂对全身和组织铁稳态和炎症产生不同的影响。我们的结果表明，两种铁补充剂均可改善 ACD/IDA 中的 Hb，但对具有明显炎症的 ACD 无效，并且在后一种情况下，静脉注射铁被困在巨噬细胞中，可能会加剧炎症。