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Down-regulation of hepcidin resulting from long-term treatment with an anti-IL-6 receptor antibody (tocilizumab) improves anemia of inflammation in multicentric Castleman disease.

Authors
  • Song, Soken-Nakazawa J
  • Tomosugi, Naohisa
  • Kawabata, Hiroshi
  • Ishikawa, Takayuki
  • Nishikawa, Teppei
  • Yoshizaki, Kazuyuki
Type
Published Article
Journal
Blood
Publisher
American Society of Hematology
Publication Date
Nov 04, 2010
Volume
116
Issue
18
Pages
3627–3634
Identifiers
DOI: 10.1182/blood-2010-03-271791
PMID: 20644113
Source
Medline
License
Unknown

Abstract

Dysregulated production of hepcidin is implicated in anemia of inflammation, whereas interleukin-6 (IL-6) is a major inducer of hepcidin production. Overproduction of IL-6 is responsible for pathogenesis of multicentric Castleman disease (MCD), a rare lymphoproliferative disorder accompanied by systemic inflammatory responses and anemia. In this study, we investigated the roles of hepcidin and IL-6 in anemia of inflammation and the long-term effects of anti-IL-6 receptor antibody (tocilizumab) treatment on serum hepcidin and iron-related parameters in MCD patients. We found that tocilizumab treatment resulted in a rapid reduction of serum hepcidin-25 in 5 of 6 MCD patients. Long-term reductions, accompanied by progressive normalization of iron-related parameters and symptom improvement, were observed in 9 of 9 cases 1.5, 3, 6, and 12 months after the start of tocilizumab treatment. In in vitro experiments, IL-6-induced up-regulation of hepcidin mRNA in hepatoma cell lines was completely inhibited by tocilizumab but increased in the presence of patients' sera. Our results suggest that, although multiple factors affect serum hepcidin levels, IL-6 plays an essential role in the induction of hepcidin in MCD. This accounts for the long-term ameliorative effect of IL-6 blockage with tocilizumab on anemia by inhibiting hepcidin production in MCD patients.

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