Does Iron Modulate Cytokine Production by Desferrioxamine Treated Mononuclear Cells?

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.

The Task of Desferrioxamine and Iron in the Immune Interplay between mononuclears and Colon Cancer Cells

“…In our hands DFO, at all three concentrations applied in the study, exerted a significant proliferation inhibition on RKO cells only. As for the effect of DFO on human PBMC it has been examined and reported in a previous work [17] . In short, DFO caused an enhanced dose dependent production of IL-1β, IL-6 and IL-1ra, whereas that of IL-2 and IFNγ was lowered.…”

“…Therefore, in order to evaluate the role of iron in the cross talk between PBMC and colon carcinoma cells from the two lines, we removed first the iron from the culture containing PBMC and the cancer cells using various concentrations of DFO. However, we had to considerate that DFO, similarly to iron, is tightly involved in both immunological and anti-proliferative events [16][17][18] . Indeed, addition of DFO to PBMC incubated with HT-29 cancer cells caused inhibition in TNFα, IFNγ, IL-1ra and IL-10 secretion, i.e.…”

“…These results point out to the capacity of DFO to affect differently the immune cross-talk between PBMC and colon cancer cells from the two lines used in this work. Studies have shown that DFO may modulate cytokine production by a number of cytokine producing cells [17] and it has a marked anti-cancer effect [19] . A pronounced blockade of IL-6 production was one of the noticeable findings in pigs undergoing acute hepatic ischemia followed by an improvement of sepsis inflammatory response and multiple organ dysfunctions [20] .…”

“…Furthermore, DFO exerts an anti-proliferative effect on cancer cells [16] . Since in a previous study we have examined the effect of iron on cytokine production by desferrioxamine treated mononuclears [17] , the present work was conceived to detect the effect of iron and DFO on the immune dialogue between human peripheral blood mononuclear cells (PBMC) and cells from HT-29 and RKO human colon cancer lines.…”