The Effect of IL‐6 in the Anemia of Inflammation

Abstract

Anemia of inflammation (AI anemia of chronic disease), results from a large variety of inflammatory conditions. Hepcidin, the principal systemic iron regulatory hormone, is increased during inflammation and limits the availability of iron for erythropoiesis. IL‐6, an inflammatory cytokine, has been shown to be necessary for the elevation of hepcidin during acute inflammation (Nemeth et al, Blood, 2004). However, it has been shown that IL‐1 can also induce hepcidin in vitro (Lee et al, PNAS, 2005). To explore whether IL‐6 is necessary for the development of AI we used a mouse model of AI induced by a single IP injection of complete Freund's adjuvant in IL‐6 KO and WT mice. Hemoglobin concentration decreased to the same extent in WT and KO mice. Hepcidin increased in WT mice but did not change in KO mice. Mean corpuscular volume (MCV) decreased in WT mice but increased in KO mice. Hepatic serum amyloid A mRNA, a marker of hepatic IL‐6 responsiveness, increased in WT but not IL‐6 KO mice indicating that the anemia was not a result of IL‐6‐like cytokines. IL‐6 is not necessary to develop AI. However, IL‐6 does effect the handling of iron as evidenced by the difference in cell size and hepcidin production.