title: Impact of individual intravenous iron preparations on the differentiation of monocytes towards macrophages and dendritic cells.
abstract: Treatment of iron deficiency with intravenous (i.v.) iron is a first-line strategy to improve anaemia of chronic kidney disease. Previous in vitro experiments demonstrated that different i.v. iron preparations inhibit differentiation of haematopoietic stem cells to monocytes, but their effect on monocyte differentiation to macrophages and mature dendritic cells (mDCs) has not been assessed. We investigated substance-specific effects of iron sucrose (IS), sodium ferric gluconate (SFG), ferric carboxymaltose (FCM) and iron isomaltoside 1000 (IIM) on monocytic differentiation to M1/M2 macrophages and mDCs.
  
  
  
  Via flow cytometry and microRNA (miRNA) expression analysis, we morphologically and functionally characterized monocyte differentiation to M1/M2 macrophages and mDCs after monocyte stimulation with IS, SFG, FCM and IIM (0.133, 0.266 and 0.533 mg/mL, respectively). To assess potential clinical implications, we compared monocytic phagocytosis capacity in dialysis patients who received either 500 mg IS or IIM.
  
  
  
  Phenotypically, IS and SFG dysregulated the expression of macrophage (e.g. CD40, CD163) and mDC (e.g. CD1c, CD141) surface markers. Functionally, IS and SFG impaired macrophage phagocytosis capacity. Phenotypic and functional alterations were less pronounced with FCM, and virtually absent with IIM. In miRNA expression analysis of mDCs, IS dysregulated miRNAs such as miR-146b-5p and miR-155-5p, which are linked to Toll-like receptor and mitogen-activated protein kinase signalling pathways. In vivo, IS reduced monocytic phagocytosis capacity within 1 h after infusion, while IIM did not.
  
  
  
  This study demonstrates that less stable i.v. iron preparations specifically affect monocyte differentiation towards macrophages and mDCs.
authors.affiliation: Department of Internal Medicine IV - Nephrology and Hypertension, Saarland University Medical Center, Homburg, Germany.
authors.forename: Lisa H
authors.initials: LH
authors.lastname: Fell
authors.affiliation: Department of Internal Medicine IV - Nephrology and Hypertension, Saarland University Medical Center, Homburg, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Seiler-Mußler
authors.affiliation: Department of Internal Medicine IV - Nephrology and Hypertension, Saarland University Medical Center, Homburg, Germany.
authors.forename: Alexander B
authors.initials: AB
authors.lastname: Sellier
authors.affiliation: GenXPro, Frankfurt am Main, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Rotter
authors.affiliation: GenXPro, Frankfurt am Main, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Winter
authors.affiliation: Department of Transplant and Infection Immunology, Saarland University Medical Center, Homburg, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Sester
authors.affiliation: Department of Internal Medicine IV - Nephrology and Hypertension, Saarland University Medical Center, Homburg, Germany.
authors.forename: Danilo
authors.initials: D
authors.lastname: Fliser
authors.affiliation: Department of Internal Medicine IV - Nephrology and Hypertension, Saarland University Medical Center, Homburg, Germany.
authors.forename: Gunnar H
authors.initials: GH
authors.lastname: Heine
authors.affiliation: Department of Internal Medicine IV - Nephrology and Hypertension, Saarland University Medical Center, Homburg, Germany.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Zawada
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000187:drug effects*; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004187:Disaccharides / Q000008:administration & dosage / Q000494:pharmacology; D005290:Ferric Compounds / Q000008:administration & dosage / Q000494:pharmacology; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid / Q000008:administration & dosage / Q000494:pharmacology; D006397:Hematinics / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D007275:Injections, Intravenous; D058085:Iron Compounds / Q000008:administration & dosage* / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008320:Maltose / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D035683:MicroRNAs / Q000235:genetics; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects
chemical_list: D004187:Disaccharides; D005290:Ferric Compounds; D006397:Hematinics; D058085:Iron Compounds; D035683:MicroRNAs; C557707:iron isomaltoside 1000; C522335:ferric carboxymaltose; D008320:Maltose; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid; C035552:ferric gluconate
keywords: CKD; dendritic cells; immune deficiency; iron therapy; macrophages