Neuer Blick auf ein altes Element – Eisen, Hepcidin und Entzündung

Zusammenfassung

Eisen (Fe) ist ein essenzielles Spurenelement und nimmt in der tierärztlichen Praxis insbesondere durch seine Bedeutung bei der Eisenmangelanämie einen wichtigen Platz ein. Die Fe-Bereitstellung, z. B. für die Hämoglobinsynthese, stellt hohe Anforderungen an die Eisenhomöostase. Mit der Charakterisierung des Hepcidins als regulatives Protein des Eisenstoffwechsels wurde deutlich, dass Fe einer hormonähnlichen Regulation unterliegt. In der Leber gebildetes Hepcidin reguliert den membranständigen Fe-Transporter Ferroportin. Ein Anstieg der Hepcidinkonzentration führt zu einer Reduzierung der Abgabe von intrazellulär gespeichertem Fe in den Extrazellulärraum. Diese Internalisierung von Fe erfolgt vor allem im retikuloendothelialen System und in Monozyten/Makrophagen, aber auch die enterale Fe-Absorption wird durch Hepcidin vermindert. Auslöser für die hepatische Hepcidinsynthese sind nach derzeitiger Sicht einerseits hohe Fe- bzw. Transferrinkonzentrationen im Plasma. Aber auch Entzündungsmediatoren wie Zytokine führen zur gesteigerten Hepcidinsynthese. Hiermit wurde ein Erklärungsansatz für die oft beobachtete deutliche Abnahme der Fe-Konzentration im Plasma im Rahmen akuter Entzündungen entwickelt, der Mechanismus wird als sog. Zytokin-Hepcidin-Link bezeichnet. Da viele pathogene Mikroorganismen Fe für ihren eigenen Stoffwechsel benötigen, wird die über Hepcidin vermittelte Modulation der Fe-Verfügbarkeit mit Internalisierung von Fe in den Intrazellulärraum der unspezifischen Abwehr zugeordnet. Fe-Supplementationen durch den Tierarzt oder den Landwirt greifen in diese Regulation ein, doch gibt es bisher nur wenige Studien zu den klinischen und metabolischen Auswirkungen oraler oder parenteraler Fe-Supplementierung unter Einbeziehung des Hepcidins. Diese sollte zukünftig wissenschaftlich detaillierter beschrieben werden. Möglicherweise resultiert daraus eine Neubewertung der verschiedenen Formen der Fe-Gabe an Wiederkäuer, Schweine und/oder Pferde.

Abstract

Iron (Fe) is an essential trace element. In daily veterinary practice, it plays a pivotal role e. g. due to its role in Fe deficiency anaemia. The bioavailability of Fe, for example for heme and hemoglobin synthesis, sets high demands on Fe homeostasis. The discovery of hepcidin as being an important regulative protein made a hormone-like regulation of the Fe metabolism evident. Hepcidin is synthesized by the liver and regulates the trans-membranous Fe-transporter ferroportin. An increase of hepcidin leads to a decrease of Fe export from the cell into the extracellular space, the consequence being an internalisation of Fe in the reticuloendothelial system as well as in mononuclear cells. Additionally, enteral Fe uptake decreases. The induction of hepatic hepcidin synthesis seems to be caused by high Fe- and transferrin concentrations in plasma. In addition to this, an increase of cytokines during inflammation similarly triggers hepatic hepcidin synthesis. This finding offers an explanation for the frequently observed decrease of Fe in serum/plasma during acute inflammation, the mechanism thus being termed as cytokine-hepcidin-link. Based on the fact that numerous pathogens require Fe for their own metabolism, internalisation of Fe into the intracellular compartment during inflammation has hence been categorised as being a part of the innate immunity. Iron supplementation, initiated by the veterinarian or the farmer, interferes with this regulation. Currently however, there is a lack of knowledge regarding the clinical and metabolic impacts of parenteral or oral Fe supplementation to farm animals. Therefore, the acquisition of added scientific data via prospective studies is warranted. In consequence, novel findings may lead to a reassessment of Fe supplementation strategies for ruminants, pigs and/or horses.

Schlüsselwörter

Transferrin - Ferroportin - Akute-Phase-Reaktion - Schwein - Wiederkäuer - Pferd

Key words

Transferrin - ferroportin - acute phase reaction - pig - ruminant - horse

Publikationsverlauf

Eingereicht: 12. Februar 2020
Eingereicht: 08. April 2020

Artikel online veröffentlicht:
18. Juni 2020

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