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

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.

Manipulation of the hepcidin pathway for therapeutic purposes

“…81 The same drug rapidly resolved anemia in monkeys with collagen-induced arthritis. 82 Anti-IL-6 antibody treatment in patients with renal cell carcinoma, multiple myeloma or Castleman's disease also effectively decreased hepcidin and increased hemoglobin.…”

Anemia of Inflammation (AI) Elevated Serum Hepcidin Level and Therapeutic Intravenous Administration of Iron

“…Treatment with anti-IL-6 receptor antibody (tocilizumab) reduced serum hepcidin levels and improved AI in Castleman disease [15]. These treatments should be considered in the near future.…”

“…Considering the role of pro-inflammatory cytokine IL-6 in the pathogenesis of AI, IL-6 represents an important target in AI [9,15]. Treatment with anti-IL-6 receptor antibody (tocilizumab) reduced serum hepcidin levels and improved AI in Castleman disease [15].…”

Frailty: Diagnosis and management

“…Development of therapeutic antibodies to hepcidin are enthusiastically awaited. Meanwhile a small study in Castleman syndrome showed improvement in anemia with the use of an interleukin-6 antibody (96).…”