Abstract

Anemia associated with inflammation or chronic disease (AICD) is a mild, normocytic, normochromic anemia that is additionally characterized by a blunted response of erythroid precursors to erythropoietin, decreased erythrocyte survival, adequate or increased iron in macrophages, and low serum iron. AICD is classically associated with chronic disease states that generate systemic inflammatory mediators, including rheumatoid arthritis, infections, severe trauma, congestive heart failure, chronic renal failure, and cancer. Many laboratory animal models of AICD have been developed based on relatively short periods of inflammation (less than 24 hours) and resulting hypoferremia. To investigate the anemia associated with chronic inflammation, we induced experimental chronic sterile abscess in C57BL/6 mice. Three weeks of abscess resulted in a mild anemia similar to that of mice with chronic over-expression of the hepcidin (hepc) transgene, but additionally characterized by moderately elevated interleukin-6 production. We previously found hepc transgenic mice have significantly reduced serum iron and non-heme liver iron concentrations, but we found no significant reduction in serum iron concentration or liver non-heme iron stores in mice with abscess at this time point. To better understand changes in erythroid precursor development in the sterile abscess model, we analyzed markers of erythroid maturation in mouse bone marrow. Flow cytometric analysis of bone marrow erythroid progenitor-precursors revealed elevated mean CD71 expression in Ter119+CD71+ precursors from mice with sterile abscess as compared to controls. This result suggests a greater proportion of Ter119+CD71+ precursors are less mature in mice with abscess. These data support the hypothesis that chronic inflammation may continue to inhibit maturation of erythroid precursors even after iron sequestration is relieved. Mice with sterile abscess are a valuable in vivo model for assessment of the various regulatory systems contributing to AICD.

Disclosures: Roy: Genzyme Corporation: stockholder; Dyax Corporation: stockholder; GTC Biotherapeutics, Inc.: stockholder; Lentigen Corporation: stockholder.

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