Acute immunomodulatory effects of iron polyisomaltosate in rats.
Anti-anaemic drug ferric-sorbitol citrate showed immunomodulatory effects, activating NF-kappaB in peritoneal macrophages, which consequently secrete tumour necrosis factor-alpha (TNF-alpha). TNF-alpha activates NF-kappaB in spleen cells. The aim of this study was to investigate the effect of iron polyisomaltosate, an iron (Fe(3+)) compound, on serum iron, interleukin-6 (IL-6) and serotonin (5-HT) concentration, neutrophil activity, and NF-kappaB activation in peritoneal macrophages and spleen cells in rats. Female Wistar rats were injected i.p. with 7.5mg iron/kg of iron polyisomaltosate 1.5, 3, 6, 24 and 48h 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-kappaB expression/activation by a Dot-Blot method. Iron polyisomaltosate significantly increased serum iron and 5-HT concentrations during the first 6h, IL-6 levels 3 and 6h, and diminished respiratory burst of granulocytes 1.5h after the injection. Iron polyisomaltosate stimulated activation of p65, p50 and RelB subunits of NF-kappaB in the peritoneal macrophages after 6h, and RelB subunit was additionally increased after 24 and 48h. In the spleen cells iron polyisomaltosate stimulated p65 subunit after 48h and RelB subunit after 24h. The results showed time-dependent immunomodulatory effects of iron polyisomaltosate. These effects might be achieved via induction of the intracellular signalling for NF-kappaB 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.
Poljak-Blazi
Marija
M
Division of Molecular Medicine, Laboratory for Oxidative Stress, Rudjer Boskovic Institute, Zagreb, Croatia.
Jaganjac
Morana
M
Mustapic
Maja
M
Pivac
Nela
N
Muck-Seler
Dorotea
D
D000818:Animals; D005260:Female; D005290:Ferric Compounds / Q000494:pharmacology*; D007155:Immunologic Factors / Q000494:pharmacology*; D015850:Interleukin-6 / Q000097:blood; D007501:Iron / Q000097:blood; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology*; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D011134:Polysaccharides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000097:blood
D005290:Ferric Compounds; D007155:Immunologic Factors; D015850:Interleukin-6; D016328:NF-kappa B; D011134:Polysaccharides; C539743:iron polyisomaltosate; D012701:Serotonin; D007501:Iron