Iron absorption and distribution in TNFΔARE/+ mice, a model of chronic inflammation

Hemizygous TNF Delta ARE/+ mice are a murine model for chronic inflammation. We utilized these animals to study iron-kinetics and corresponding protein expression in an iron-deficient and iron-adequate setting. Fe-59-absorption was determined in ligated duodenal loops in vivo. Whole body distribution of i.v. injected Fe-59 was analysed, and the organ specific expression of ferroportin, transferrin receptor-1, hepcidin and duodenal DMT-1 was quantified by real-time PCR and Western blotting. Duodenal Fe-59-lumen-to-body transport was not affected by the genotype. Duodenal Fe-59-retention was increased in TNF Delta ARE/+ mice, suggesting higher Fe-59-losses with defoliated enterocytes. Iron-deficiency increased duodenal Fe-59-lumen-to-body transport, and higher duodenal Fe-59-tissue retention went along with higher duodenal DMT-1, ferroportin, and liver hepcidin expression. TNF Delta ARE/+ mice significantly increase their Fe-59-content in inflamed joints and ilea, and correspondingly reduce splenic Fe-59-content. Leukocyte infiltrations in the joints suggest a substantial shift of iron-loaded RES cells to inflamed tissues as the underlying mechanism. This finding was paralleled by increased non-haem iron content in joints and reduced haemoglobin and haematocrit concentrations in TNF Delta ARE/+, mice. In conclusion, erythropoiesis in inflamed TNF Delta ARE/+ mice could be iron-limited due to losses with exfoliated iron-loaded enterocytes and/or to increased iron-retention in RES cells that shift from the spleen to inflamed tissues. (C) 2009 Elsevier GmbH. All rights reserved.