Effect of different intravenous iron preparations on lymphocyte intracellular reactive oxygen species generation and subpopulation survival.
BACKGROUND
Infections in hemodialysis (HD) patients lead to high morbidity and mortality rates and are associated with early cardiovascular mortality, possibly related to chronic inflammation. Intravenous (IV) iron is widely administered to HD patients and has been associated with increased oxidative stress and dysfunctional cellular immunity. The purpose of this study was to examine the effect of three commercially available IV iron preparations on intracellular reactive oxygen species generation and lymphocyte subpopulation survival.


METHODS
Peripheral blood mononuclear cells (PBMC) were isolated from healthy donor buffy coat. PBMC were cultured and incubated with 100 microg/mL of sodium ferric gluconate (SFG), iron sucrose (IS) or iron dextran (ID) for 24 hours. Cells were then probed for reactive oxygen species (ROS) with dichlorofluorescein-diacetate. In separate studies, isolated PBMCs were incubated with the 25, 50 or 100 microg/mL iron concentrations for 72 hours and then stained with fluorescein conjugated monoclonal antibodies for lymphocyte subpopulation identification. Untreated PBMCs at 24 hours and 72 hours served as controls for each experiment.


RESULTS
All three IV iron preparations induced time dependent increases in intracellular ROS with SFG and IS having a greater maximal effect than ID. The CD4+ lymphocytes were most affected by IV iron exposure, with statistically significant reduction in survival after incubation with all three doses (10, 25 and 100 microg/mL) of SFG, IS and ID.


CONCLUSIONS
These data indicate IV iron products induce differential deleterious effects on CD4+ and CD16+ human lymphocytes cell populations that may be mediated by intracellular reactive oxygen species generation. Further studies are warranted to determine the potential clinical relevance of these findings.
Gupta
Ajay
A
Rockwell Medical, Wixom, MI, USA. agupta@rockwellmed.com
Zhuo
Jiaying
J
Zha
Junli
J
Reddy
Srinivasa
S
Olp
Jonathan
J
Pai
Amy
A
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005290:Ferric Compounds / Q000633:toxicity*; D000077605:Ferric Oxide, Saccharated; D058851:GPI-Linked Proteins; D005937:Glucaric Acid; D006801:Humans; D007505:Iron-Dextran Complex / Q000633:toxicity*; D016131:Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008970:Molecular Weight; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D017452:Receptors, IgG / Q000032:analysis; D013395:Sucrose / Q000633:toxicity*
C428200:FCGR3B protein, human; D005290:Ferric Compounds; D058851:GPI-Linked Proteins; D017382:Reactive Oxygen Species; D017452:Receptors, IgG; D013395:Sucrose; D007505:Iron-Dextran Complex; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid; C035552:ferric gluconate