Does Iron Modulate Cytokine Production by Desferrioxamine Treated Mononuclear Cells?

Hanna Bessler,Meir Djaldetti

doi:10.3844/ojbsci.2018.108.114

Abstract

Iron is an essential element for maintaining the normal function of cellular and multicellular organisms and it is closely associated with inflammation and immunity. Macrophages and lymphocytes play an important role in its homeostasis. Hereby we have evaluated cytokine production by iron depleted and iron supplemented human peripheral blood mononuclear cells (PBMC) from healthy adult donors. Non-stimulated or stimulated PBMC (lipopolysaccharide-LPS or phorbol-myristate acetate-PMA and ionomycin) were incubated for 24 h without or with desferrioxamine (DFO) and the quantity of TNFα, IL-1β, IL-6, IFNγ, IL-2, IL-10 and IL-1ra in the supernatants was evaluated using ELISA kits. In addition, cytokine levels were determined in supernatants of cultures to which DFO was added for 2 h followed by 24 h of incubation with iron. The secretion of IL-1β, IL-6 and IL-1ra by non-stimulated PBMC and that of IL-1β by LPS-stimulated cells was dose-dependently enhanced following incubation with increasing concentrations of DFO between 25 and 100 µM. On the other hand LPS-induced production of IL-10 and PMA/ionomycin stimulated IL-2 and IFNγ secretion was dose dependently reduced. The inhibited IFNγ, IL-2 and IL-10 secretion by stimulated PBMC caused by DFO was reversed after incubation with iron at concentrations similar to those in human serum. However, the inhibition of LPS-induced IL-1ra or IL-1β production induced by DFO was not affected by iron supplementation. The results of the study underline the importance of intra and/or extracellular iron concentration and DFO for the release of inflammatory cytokines by human peripheral blood mononuclear cells.

Highlights

The potential of iron as a source of strength has been known to the ancient Greeks and it was introduced in the seventeen century as a therapeutic agent for iron deficiency anemia (Powers and Buchanan, 2014)
While ferroportin exports iron from the macrophages, hepcidin, which is synthesized in the liver, blocks iron release from the cells and prevents its absorption from duodenal enterocytes with a subsequent development of iron deficiency and anemia (Michels et al, 2015; Ganz and Nemeth, 2015; Grellier et al, 2015; Smith et al, 2013)
At DFO concentrations of 50 μM and 100 μM the production of IL-1β by non-stimulated peripheral blood mononuclear cells (PBMC) increased by 35% (NS) and 54% (p

Summary

Introduction

The potential of iron as a source of strength has been known to the ancient Greeks and it was introduced in the seventeen century as a therapeutic agent for iron deficiency anemia (Powers and Buchanan, 2014). Hepcidin and ferroportin mediate the iron flux into bacteria resulting in disturbances in bacterial growth (Ward et al, 2011), whereas iron accumulation in the macrophages is the base of their bacteriostatic capacity (Recalcati et al, 2012). The generation of the same cytokines was evaluated following addition of iron to DFO treated cells

Methods

Results

Conclusion