Tumour necrosis factor alpha causes hypoferraemia and reduced intestinal iron absorption in mice
Résumé
Cytokines are implicated in the anaemia of chronic disease by reducing erythropoiesis and increasing iron sequestration in the reticuloendotheial system. However, the effect of cytokines in particular TNF-{alpha} on small bowel iron uptake and iron transporter expression remains unclear. In this study we subjected CD1 male mice to intra-peritoneal injection with TNF-{alpha} (10ng/mouse) and then examined the expression and localisation of DMT1, Ireg1, and ferritin in duodenum. Liver and spleen samples were used to determine hepcidin mRNA expression. Changes in serum iron and iron loading of duodenum, spleen and liver were also determined. We report in this study a significant fall in serum iron 3 hours post TNF-{alpha} exposure (p<0.05). This was co-incident with increased iron deposition in the spleen. After 24 hours exposure there was a significant decrease in duodenal iron transfer (p<0.05) co-incident with increased enterocyte ferritin expression (p<0.05) and re-localisation of Ireg1 from the basolateral enterocyte membrane. Hepatic hepcidin mRNA levels remained unchanged whilst splenic hepcidin mRNA expression was reduced at 24hrs. In conclusion we provide evidence that TNF-{alpha} may contribute to anaemia of chronic disease by iron sequestration in the spleen and by reduced duodenal iron transfer which seems to be due to increased enterocyte iron binding by ferritin and a loss of Ireg1 function. These observations were independent of hepcidin mRNA levels.
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