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Nephrol Dial Transplant. 2016 Nov;31(11):1835-1845. Epub 2016 Mar 24.

Impact of individual intravenous iron preparations on the differentiation of monocytes towards macrophages and dendritic cells.

Author information

1
Department of Internal Medicine IV - Nephrology and Hypertension, Saarland University Medical Center, Homburg, Germany.
2
GenXPro, Frankfurt am Main, Germany.
3
Department of Transplant and Infection Immunology, Saarland University Medical Center, Homburg, Germany.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

This study demonstrates that less stable i.v. iron preparations specifically affect monocyte differentiation towards macrophages and mDCs.

KEYWORDS:

CKD; dendritic cells; immune deficiency; iron therapy; macrophages

PMID:
27190361
PMCID:
PMC5091613
DOI:
10.1093/ndt/gfw045
[Indexed for MEDLINE]
Free PMC Article

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