Effect of different intravenous iron preparations on lymphocyte intracellular reactive oxygen species generation and subpopulation survival

Peripheral blood mononuclear cells (PBMC) were isolated from healthy donor buffy coat. PBMC were cultured and incubated with 100 μg/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 μg/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.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 μg/mL) of SFG, IS and ID.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.Infection is the second leading cause of mortality among hemodialysis (HD) patients. Infections in HD patients are also associated with increased cardiovascular mortality, which may be related to immune system dysfunction resulting in recurrent infections that contribute to chronic inflammation and accelerated atherosclerosis [1]. Cellular dysfunction of both innate (e.g. T cells and macrophages) and adaptive (e.g. B cells) immunity is well described in patients with chronic kidney disease (CKD) and may be attributable to many factors including accumulated uremic toxin burden, bio-incompatible dialysis membranes, anemia, malnutrition and altered iron metabolism [1,2].Transfusional iron overload has long been linked with immune dysfunctio