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      Iron deficiency or anemia of inflammation? : Differential diagnosis and mechanisms of anemia of inflammation Translated title: Eisenmangel oder Entzündungsanämie? : Differenzialdiagnose und Mechanismen der Entzündungsanämie

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          Summary

          Iron deficiency and immune activation are the two most frequent causes of anemia, both of which are based on disturbances of iron homeostasis. Iron deficiency anemia results from a reduction of the body’s iron content due to blood loss, inadequate dietary iron intake, its malabsorption, or increased iron demand. Immune activation drives a diversion of iron fluxes from the erythropoietic bone marrow, where hemoglobinization takes place, to storage sites, particularly the mononuclear phagocytes system in liver and spleen. This results in iron-limited erythropoiesis and anemia. This review summarizes current diagnostic and pathophysiological concepts of iron deficiency anemia and anemia of inflammation, as well as combined conditions, and provides a brief outlook on novel therapeutic options.

          Zusammenfassung

          Eisenmangel und Immunaktivierung sind die zwei häufigsten Ursachen der Anämie. In beiden Situationen besteht ursächlich eine Störung der Eisenhomöostase. Die Eisenmangelanämie beruht auf einer Verminderung des Gesamtkörpereisens infolge von Blutverlust, unzureichender alimentärer Zufuhr oder intestinaler Absorption bzw. erhöhtem Bedarf an Eisen. Immunaktivierung führt bei normalem Gesamtkörpereisen zu dessen Umverteilung vom erythropoetischen Knochenmark, der primären Stelle der Hämoglobinproduktion, in das mononukleäre Phagozytensystem der Leber und Milz, die Hauptorgane der Eisenspeicherung. Dies führt letztlich zur Anämie. In dem vorliegenden Übersichtsartikel werden aktuelle diagnostische und pathophysiologische Konzepte von Eisenmangelanämie, Entzündungsanämie sowie kombinierter Anämie zusammengefasst und ein kurzer Ausblick auf neue Therapieoptionen geboten.

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          Most cited references139

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          Bacterial iron homeostasis.

          Iron is essential to virtually all organisms, but poses problems of toxicity and poor solubility. Bacteria have evolved various mechanisms to counter the problems imposed by their iron dependence, allowing them to achieve effective iron homeostasis under a range of iron regimes. Highly efficient iron acquisition systems are used to scavenge iron from the environment under iron-restricted conditions. In many cases, this involves the secretion and internalisation of extracellular ferric chelators called siderophores. Ferrous iron can also be directly imported by the G protein-like transporter, FeoB. For pathogens, host-iron complexes (transferrin, lactoferrin, haem, haemoglobin) are directly used as iron sources. Bacterial iron storage proteins (ferritin, bacterioferritin) provide intracellular iron reserves for use when external supplies are restricted, and iron detoxification proteins (Dps) are employed to protect the chromosome from iron-induced free radical damage. There is evidence that bacteria control their iron requirements in response to iron availability by down-regulating the expression of iron proteins during iron-restricted growth. And finally, the expression of the iron homeostatic machinery is subject to iron-dependent global control ensuring that iron acquisition, storage and consumption are geared to iron availability and that intracellular levels of free iron do not reach toxic levels.
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            Iron homeostasis in host defence and inflammation.

            Iron is an essential trace element for multicellular organisms and nearly all microorganisms. Although iron is abundant in the environment, common forms of iron are minimally soluble and therefore poorly accessible to biological organisms. Microorganisms entering a mammalian host face multiple mechanisms that further restrict their ability to obtain iron and thereby limit their pathogenicity. Iron levels also modulate host defence, as iron content in macrophages regulates their cytokine production. Here, we review recent advances that highlight the role of systemic and cellular iron-regulating mechanisms in protecting hosts from infection, emphasizing aspects that are applicable to human health and disease.
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              Iron and microbial infection.

              The use of iron as a cofactor in basic metabolic pathways is essential to both pathogenic microorganisms and their hosts. It is also a pivotal component of the innate immune response through its role in the generation of toxic oxygen and nitrogen intermediates. During evolution, the shared requirement of micro- and macroorganisms for this important nutrient has shaped the pathogen-host relationship. Here, we discuss how pathogens compete with the host for iron, and also how the host uses iron to counteract this threat.
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                Author and article information

                Contributors
                manfred.nairz@i-med.ac.at
                guenter.weiss@i-med.ac.at
                Journal
                Wien Med Wochenschr
                Wien Med Wochenschr
                Wiener Medizinische Wochenschrift (1946)
                Springer Vienna (Vienna )
                0043-5341
                1563-258X
                24 August 2016
                24 August 2016
                2016
                : 166
                : 13
                : 411-423
                Affiliations
                [1 ]Department of Internal Medicine VI, Infectious Diseases, Immunology, Rheumatology, Pneumology, Medical University of Innsbruck, Anichstraße 35, 6020 Innsbruck, Austria
                [2 ]Medical Clinic III, Department of Oncology, Hematology and Rheumatology, University Clinic Bonn (UKB), Bonn, Germany
                Article
                505
                10.1007/s10354-016-0505-7
                5065583
                27557596
                7c56f032-da71-45da-bb26-1bdcd6622cb8
                © The Author(s) 2016

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 19 January 2016
                : 30 May 2016
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                © Springer-Verlag Wien 2016

                Medicine
                anemia of inflammation,anemia of chronic disease,iron,hepcidin,macrophage,entzündungsanämie,anämie bei chronischer erkrankung,eisen,makrophage

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