The Lynx Group

The Role of Hepcidin in Multicentric Castleman Disease

Conference Correspondent

Dysregulated production of hepcidin is implicated in anemia of inflammation, and IL-6 is a major inducer of hepcidin production. Increased inflammatory cytokines, especially IL-6, are responsible for the pathogenesis of MCD and rheumatoid arthritis. At a study presented at ASH 2014, Yoshizaki and colleagues studied the role of hepcidin and IL-6 in patients with anemia of inflammation and MCD or rheumatoid arthritis by investigating the effect of tocilizumab, an anti–IL-6 receptor antibody, on serum hepcidin and the relationship between hepcidin and iron-related parameters (Yoshizaki K, et al. Blood. 2014;124. Abstract 4006).

The mechanism involving inflammatory anemia in patients with MCD and rheumatoid arthritis was further analyzed in vitro by studying the transcriptional regulation of hepcidin in hepatoma-derived cell lines in the presence of cytokines, antibodies against cytokines, inhibitors of signal pathways, and other hematopoietic factors.

The data showed that treatment with tocilizumab resulted in a rapid reduction of serum hepcidin-25 in patients with MCD and rheumatoid arthritis. Furthermore, long-term reductions (>1 year) of hepcidin-25 were observed in 10 cases of MCD after treatment with tocilizumab, accompanied by progressive normalization of iron-related parameters and improved disease activity. In in vitro experiments, IL-6, but not tumor necrosis factor-? or IL-1, induced the upregulation of hepcidin mRNA in hepatoma cell lines that was completely inhibited with tocilizumab, but enhanced by BMP4 and the serum from a patient with MCD.

These results suggest that, although multiple factors affect serum hepcidin levels, IL-6 plays an essential role in the induction of hepcidin; thus, the long-term ameliorative effect of IL-6 blockade with tocilizumab on anemia is through the inhibition of hepcidin production in patients with MCD and rheumatoid arthritis.

Related Articles

Subscribe Today!

To sign up for our newsletter or print publications, please enter your contact information below.

I'd like to receive: