Page 61 - 2019_06-Haematologica-web

Iron Metabolism & its Disorders
The opposing effects of acute inflammation and iron deficiency anemia on serum hepcidin and iron absorption in young women
Ferrata Storti Foundation
Haematologica 2019 Volume 104(6):1143-1149
Nicole U. Stoffel,1 Meryem Lazrak,2 Souhaila Bellitir,2 Nissrine El Mir,2 Asmaa El Hamdouchi,2 Amina Barkat,3 Christophe Zeder,1 Diego Moretti,1 Hassan Aguenaou2 and Michael B. Zimmermann1
1ETH Zürich, Laboratory of Human Nutrition, Institute of Food Nutrition and Health, Department of Health Science and Technology, Zürich, Switzerland; 2Ibn Tofaïl University- CNESTEN, Joint Research Unit in Nutrition and Food, RDC-Nutrition AFRA/IAEA, Rabat- Kénitra, Morocco and 3Mohamed V University, Unit of Research on Nutrition and Health of Mother and Nutrition, Faculty of Medicine and Pharmacy, Rabat, Morocco
ABSTRACT
Hepatic hepcidin synthesis is stimulated by inflammation but inhibit- ed during iron deficiency anemia (IDA). In humans, the relative strength of these opposing signals on serum hepcidin and the net effect on iron absorption and systemic iron recycling is uncertain. In this prospective, 45-day study, in young women (n=46; age 18-49 years) with or without IDA, we compared iron and inflammation markers, serum hep- cidin and erythrocyte iron incorporation from 57Fe-labeled test meals, before and 8, 24 and 36 hours (h) after influenza/DPT vaccination as an acute inflammatory stimulus. Compared to baseline, at 24-36 h after vaccination: 1) interleukin-6 increased 2-3-fold in both groups (P<0.001); 2) serum hep- cidin increased >2-fold in the non-anemic group (P<0.001), but did not sig- nificantly change in the IDA group; 3) serum iron decreased in the non-ane- mic group (P<0.05) but did not change in the IDA group; and 4) erythrocyte iron incorporation did not change in either of the two groups, but was approximately 2-fold higher in the IDA group both before and after vacci- nation (P<0.001). In this study, mild acute inflammation did not increase serum hepcidin in women with IDA, suggesting low iron status and ery- thropoietic drive offset the inflammatory stimulus on hepcidin expression. In non-anemic women, inflammation increased serum hepcidin and pro- duced mild hypoferremia, but did not reduce dietary iron absorption, sug- gesting iron-recycling macrophages are more sensitive than the enterocyte to high serum hepcidin during inflammation. The study was registered as a prospective observational trial at clinicaltrials.gov identifier: 02175888. The study was funded by the International Atomic Energy Agency.
Introduction
The hepatic hormone hepcidin regulates serum iron concentrations and iron homeostasis.1 Hepcidin synthesis is stimulated by high liver iron stores, high plas- ma iron concentrations and inflammation, and is inhibited by hypoxia and erythro- poietic drive.1 In conditions such as the iron-loading anemias, the anemia of chronic disease, and acute infection during iron deficiency anemia (IDA), several of these factors simultaneously generate opposing signals on hepcidin expression. The rela- tive strength of these opposing signals to regulate serum hepcidin (SHep) in humans is uncertain.
Iron-deficient mice up-regulate hepcidin expression when injected with lipopolysaccharide (LPS) to induce inflammation.2 Other animal studies suggest erythroid demand for iron is a stronger regulator of hepcidin expression than inflammation.3-5 Most human studies examining opposing stimuli on SHep have been descriptive; some have suggested that iron status and/or erythropoiesis are the major regulators of SHep,4,6,7 others suggest inflammation is associated with
Correspondence:
NICOLE U. STOFFEL
nicole.stoffel@hest.ethz.ch
Received: October 8, 2018. Accepted: January 2, 2019. Pre-published: January 10, 2019.
doi:10.3324/haematol.2018.208645
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/6/1143
©2019 Ferrata Storti Foundation
Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or inter- nal use. Sharing published material for non-commercial pur- poses is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for com- mercial purposes is not allowed without permission in writing from the publisher.
haematologica | 2019; 104(6)
1143
ARTICLE