PURPOSE: Hepcidin is a liver-produced peptide implicated in the anemia of inflammation. Because interleukin (IL)-6 is a potent inducer of hepcidin expression and its levels are elevated in multiple myeloma, we studied the role of hepcidin in the anemia of multiple myeloma. EXPERIMENTAL DESIGN: Urinary hepcidin and serum levels of IL-6, ferritin, C-reactive protein, tumor necrosis factor-alpha, and IL-1 beta were studied in newly diagnosed myeloma patients. In vitro hepcidin induction assay was assessed by real-time PCR assay. RESULTS: Pretreatment urinary hepcidin levels in 44 patients with stage III multiple myeloma were 3-fold greater than normal controls. In the subset of multiple myeloma patients without renal insufficiency (n = 27), a marked inverse correlation was seen between hemoglobin at diagnosis and urinary hepcidin level (P = 0.014) strongly supporting a causal relationship between up-regulated hepcidin expression and anemia. The urinary hepcidin also significantly (P < 0.05) correlated with serum ferritin and C-reactive protein, whereas its correlation with serum IL-6 levels was of borderline significance (P = 0.06). Sera from 14 multiple myeloma patients, with known elevated urinary hepcidin, significantly induced hepcidin mRNA in the Hep3B cells, whereas normal sera had no effect. For 10 patients, the ability of anti-IL-6 and anti-IL-6 receptor antibodies to prevent the serum-induced hepcidin RNA was tested. In 6 of these patients, hepcidin induction was abrogated by the anti-IL-6 antibodies, but in the other 4 patients, the neutralizing antibodies had no effect. CONCLUSIONS: These results indicate hepcidin is up-regulated in multiple myeloma patients by both IL-6-dependent and IL-6-independent mechanisms and may play a role in the anemia of multiple myeloma.
PURPOSE:Hepcidin is a liver-produced peptide implicated in the anemia of inflammation. Because interleukin (IL)-6 is a potent inducer of hepcidin expression and its levels are elevated in multiple myeloma, we studied the role of hepcidin in the anemia of multiple myeloma. EXPERIMENTAL DESIGN: Urinary hepcidin and serum levels of IL-6, ferritin, C-reactive protein, tumor necrosis factor-alpha, and IL-1 beta were studied in newly diagnosed myelomapatients. In vitro hepcidin induction assay was assessed by real-time PCR assay. RESULTS: Pretreatment urinary hepcidin levels in 44 patients with stage III multiple myeloma were 3-fold greater than normal controls. In the subset of multiple myelomapatients without renal insufficiency (n = 27), a marked inverse correlation was seen between hemoglobin at diagnosis and urinary hepcidin level (P = 0.014) strongly supporting a causal relationship between up-regulated hepcidin expression and anemia. The urinary hepcidin also significantly (P < 0.05) correlated with serum ferritin and C-reactive protein, whereas its correlation with serum IL-6 levels was of borderline significance (P = 0.06). Sera from 14 multiple myelomapatients, with known elevated urinary hepcidin, significantly induced hepcidin mRNA in the Hep3B cells, whereas normal sera had no effect. For 10 patients, the ability of anti-IL-6 and anti-IL-6 receptor antibodies to prevent the serum-induced hepcidin RNA was tested. In 6 of these patients, hepcidin induction was abrogated by the anti-IL-6 antibodies, but in the other 4 patients, the neutralizing antibodies had no effect. CONCLUSIONS: These results indicate hepcidin is up-regulated in multiple myelomapatients by both IL-6-dependent and IL-6-independent mechanisms and may play a role in the anemia of multiple myeloma.
Authors: Ken Maes; Elizabeta Nemeth; G David Roodman; Alissa Huston; Flavia Esteve; Cesar Freytes; Natalie Callander; Eirini Katodritou; Lisa Tussing-Humphreys; Seth Rivera; Karin Vanderkerken; Alan Lichtenstein; Tomas Ganz Journal: Blood Date: 2010-08-02 Impact factor: 22.113
Authors: Zhimin Gu; He Wang; Jiliang Xia; Ye Yang; Zhendong Jin; Hongwei Xu; Jumei Shi; Ivana De Domenico; Guido Tricot; Fenghuang Zhan Journal: Cancer Res Date: 2015-04-08 Impact factor: 12.701
Authors: Luigi Ferrucci; Richard D Semba; Jack M Guralnik; William B Ershler; Stefania Bandinelli; Kushang V Patel; Kai Sun; Richard C Woodman; Nancy C Andrews; Robert J Cotter; Tomas Ganz; Elizabeta Nemeth; Dan L Longo Journal: Blood Date: 2010-01-15 Impact factor: 22.113
Authors: Frank Schwoebel; Lucas T van Eijk; Dirk Zboralski; Simone Sell; Klaus Buchner; Christian Maasch; Werner G Purschke; Martin Humphrey; Stefan Zöllner; Dirk Eulberg; Frank Morich; Peter Pickkers; Sven Klussmann Journal: Blood Date: 2013-01-24 Impact factor: 22.113