Acute immunomodulatory effects of iron polyisomaltosate in rats

Anti-anaemic drug ferric-sorbitol citrate showed immunomodulatory effects, activating NF-κB in peritoneal macrophages, which consequently secrete tumour necrosis factor-α (TNF-α). TNF-α activates NF-κB in spleen cells. The aim of this study was to investigate the effect of iron polyisomaltosate, an iron (Fe3+) compound, on serum iron, interleukin-6 (IL-6) and serotonin (5-HT) concentration, neutrophil activity, and NF-κB activation in peritoneal macrophages and spleen cells in rats. Female Wistar rats were injected i.p. with 7.5 mg iron/kg of iron polyisomaltosate 1.5, 3, 6, 24 and 48 h before sacrifice. Serum iron, 5-HT and IL-6 concentration was determined by colorimetric, spectrofluorimetric and ELISA methods, neutrophil activity by a chemiluminescence assay, and NF-κB expression/activation by a Dot-Blot method. Iron polyisomaltosate significantly increased serum iron and 5-HT concentrations during the first 6 h, IL-6 levels 3 and 6 h, and diminished respiratory burst of granulocytes 1.5 h after the injection. Iron polyisomaltosate stimulated activation of p65, p50 and RelB subunits of NF-κB in the peritoneal macrophages after 6 h, and RelB subunit was additionally increased after 24 and 48 h. In the spleen cells iron polyisomaltosate stimulated p65 subunit after 48 h and RelB subunit after 24 h. The results showed time-dependent immunomodulatory effects of iron polyisomaltosate. These effects might be achieved via induction of the intracellular signalling for NF-κB activation in peritoneal macrophages and later in spleen cells, together with increase of serum 5-HT, and IL-6 but with diminished respiratory burst of granulocytes. Iron polyisomaltosate presumably activated reactive oxygen species resulting in the stimulation of the acute phase reactants in the liver.