292: The role of IL-6 with TNF-α or IL-1 on induction of inflammatory anemia through hepcidin in different chronic inflammatory disease

Abstract

The association of anemia with chronic inflammatory disease, such as autoimmune disease, Castleman’s disease (CD), vasculitis, rheumatic disease (RA) and so on are well known. However, the precise mechanism of this type of anemia, chronic inflammatory anemia (CIA), is still unclear. Anemia with CD in which IL-6 induction is a main cause is severe (Hb. 7.0–10.0 g/dl), on the other hand anemia with RA in which IL-6, TNF-α and IL-1 are contributed is not so severe (Hb.9.0–11.0 g/dl). This difference is also unknown. We analyzed the induction mechanism of CIA with CD and RA by both in vitro and in vivo experiment utilizing an IL-6 blockade, anti-IL-6 antibody (tocilizumab) on induction of hepcidin which is produced from liver and inhibits Fe absorption from intestine and Fe-release from macrophage. The patients with CD and RA were treated with tocilizumab. The anemia with both CD and RA was completely normalized after the therapy. However, anti-TNF-α therapy with or without methotrexate partially improved anemia but the anemia was hardly gotten into the normal range. To know this different phenomenon between the efficacy of IL-6 and TNF-α therapy, hepcidin induction mechanism was analyzed by using hepatocyte cell lines stimulated with IL-6 and/or TNF-α.