Mechanistic and Therapeutic Studies Related to Anemia of Chronic Disease and Inflammation

Abstract

The erythroid iron restriction response (EIRR) results from lineage-selective inactivation of aconitase enzymes, causing diminished erythropoietin (Epo) responsiveness in early erythroid progenitors. Provision of exogenous isocitrate in either cell culture or murine models of iron deficiency restores Epo responsiveness and abrogates the erythropoietic block characteristic of the iron deprivation response.