title: Intravenous Iron Carboxymaltose as a Potential Therapeutic in Anemia of Inflammation.
abstract: Intravenous iron supplementation is an effective therapy in iron deficiency anemia (IDA), but controversial in anemia of inflammation (AI). Unbound iron can be used by bacteria and viruses for their replication and enhance the inflammatory response. Nowadays available high molecular weight iron complexes for intravenous iron substitution, such as ferric carboxymaltose, might be useful in AI, as these pharmaceuticals deliver low doses of free iron over a prolonged period of time. We tested the effects of intravenous iron carboxymaltose in murine AI: Wild-type mice were exposed to the heat-killed Brucella abortus (BA) model and treated with or without high molecular weight intravenous iron. 4h after BA injection followed by 2h after intravenous iron treatment, inflammatory cytokines were upregulated by BA, but not enhanced by iron treatment. In long term experiments, mice were fed a regular or an iron deficient diet and then treated with intravenous iron or saline 14 days after BA injection. Iron treatment in mice with BA-induced AI was effective 24h after iron administration. In contrast, mice with IDA (on iron deficiency diet) prior to BA-IA required 7d to recover from AI. In these experiments, inflammatory markers were not further induced in iron-treated compared to vehicle-treated BA-injected mice. These results demonstrate that intravenous iron supplementation effectively treated the murine BA-induced AI without further enhancement of the inflammatory response. Studies in humans have to reveal treatment options for AI in patients.
authors.affiliation: Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, University of Muenster, Muenster, Germany.
authors.forename: Niklas
authors.initials: N
authors.lastname: Lofruthe
authors.affiliation: Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, University of Muenster, Muenster, Germany.
authors.forename: Inka
authors.initials: I
authors.lastname: Gallitz
authors.affiliation: Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, University of Muenster, Muenster, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Traeger
authors.affiliation: Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Muenster, Muenster, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Bäumer
authors.affiliation: Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Muenster, Muenster, Germany.
authors.forename: Isabell
authors.initials: I
authors.lastname: Schulze
authors.affiliation: Institute for Neuropathology, University Hospital Muenster, University of Muenster, Muenster, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Kuhlmann
authors.affiliation: Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Muenster, Muenster, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Müller-Tidow
authors.affiliation: Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, University of Muenster, Muenster, Germany.
authors.forename: Andrea U
authors.identifier: http://orcid.org/0000-0002-5237-961X
authors.initials: AU
authors.lastname: Steinbicker
mesh_terms: D061605:Administration, Intravenous; D000740:Anemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002003:Brucella abortus / Q000502:physiology; D016207:Cytokines / Q000097:blood; D004032:Diet; D005290:Ferric Compounds / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D064451:Hepcidins / Q000378:metabolism; D007249:Inflammation / Q000150:complications; D007501:Iron / Q000097:blood; D008320:Maltose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012156:Reticulocytes / Q000187:drug effects / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines; D005290:Ferric Compounds; D064451:Hepcidins; D012333:RNA, Messenger; C522335:ferric carboxymaltose; D008320:Maltose; D007501:Iron