title: Distinct immunologic effects of different intravenous iron preparations on monocytes.
abstract: BACKGROUND
  Iron deficiency contributes to anaemia in patients with chronic kidney disease. I.v. iron is therefore widely used for anaemia treatment, although it may induce oxidative stress and activate monocytes. Different i.v. iron preparations are available, but interestingly their substance-specific immunologic effects are poorly studied.
  
  
  METHODS
  We analysed the effect of iron sucrose, ferric carboxymaltose, iron isomaltoside 1000, low-molecular-weight iron dextran and ferumoxytol on classical, intermediate and nonclassical monocyte biology. We therefore stimulated in vitro mature monocytes and haematopoietic CD34(+) stem cells during their differentiation into monocytes with different concentrations (0.133, 0.266, 0.533 mg/mL) of i.v. iron preparations. Alterations of monocyte subset distribution, expression of surface markers (CD86, CCR5, CX3CR1), as well as production of pro-inflammatory cytokines (TNF-α, IL-1β) and reactive oxygen species were measured using flow cytometry. Additionally, we analysed phagocytosis and antigen presentation capacity.
  
  
  RESULTS
  We found specific immunologic effects after stimulation with iron sucrose which were not induced by the other iron preparations. Iron sucrose activated monocyte subsets leading to significantly increased CD86 expression. Simultaneously CD16 and CX3CR1 expression and monocytic phagocytosis capacity were decreased. Additionally, differentiation of monocytes from haematopoietic CD34(+) stem cells was almost completely abolished after stimulation with iron sucrose.
  
  
  CONCLUSIONS
  Our findings demonstrate that specific immunologic effects of distinct i.v. iron preparations exist. The clinical relevance of these findings requires further investigation.
authors: Department of Internal Medicine IV - Nephrology and Hypertension, Saarland University Medical Center, Homburg, Germany.
authors: Lisa H
authors: LH
authors: Fell
authors: Adam M
authors: AM
authors: Zawada
authors: Kyrill S
authors: KS
authors: Rogacev
authors: Sarah
authors: S
authors: Seiler
authors: Danilo
authors: D
authors: Fliser
authors: Gunnar H
authors: GH
authors: Heine
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D007111:Immunity, Cellular; D007275:Injections, Intravenous; D058085:Iron Compounds / Q000008:administration & dosage*; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000276:immunology*; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology
chemical_list: D018925:Chemokines; D058085:Iron Compounds
keywords: CD14; CD16; immune deficiency; iron therapy; monocyte subsets