Anemia in Hodgkin's lymphoma: the role of interleukin-6 and hepcidin

Stefan Hohaus, Francesco D'Alo', Luigi Maria Larocca, Giuseppina Massini, Manuela Giachelia, Barbara Vannata, Valentina Bozzoli, Annarosa Cuccaro, Maria Teresa Voso, Giuseppe Leone, Reinier A. P. Raymakers, Dorine W. Swinkels

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80 Citazioni (Scopus)

Abstract

PURPOSE: Cytokines play a pivotal role in Hodgkin's lymphoma (HL). Because interleukin-6 (IL-6) induces expression of hepcidin, one of the principal regulators of iron metabolism, we studied the contribution of hepcidin in anemia in HL at diagnosis. PATIENTS AND METHODS: Plasma samples from 65 patients with HL were analyzed for hepcidin levels using a combination of weak cation exchange chromatography and time-of-flight mass spectrometry; cytokine levels were analyzed using enzyme-linked immunosorbent assays and parameters of iron metabolism and acute-phase reaction. RESULTS: Hepcidin plasma levels were significantly higher in HL patients when compared with controls, independent of the presence of anemia (P = .001). In the subset of patients with anemia, hepcidin levels inversely correlated with hemoglobin levels (P = .01). Analyzing parameters of iron metabolism, hepcidin levels showed a positive correlation with ferritin (P < .001) and an inverse correlation to iron and iron-binding capacity. Hepcidin strongly correlated to IL-6 levels (P < .001) but not to IL-10 or thymus and activation-regulated cytokine (TARC)/chemokine (C-C motif) ligand 17 (CCL17) levels. In a multivariate regression analysis, IL-6 and fibrinogen levels were independently associated with hepcidin. Higher hepcidin levels were observed in patients with more aggressive disease characteristics: stage IV disease (P = .01), presence of B symptoms (P = .03), and International Prognostic Score > 2 (P = .005). CONCLUSION: Our findings suggest that in HL, hepcidin is upregulated by IL-6. Elevated hepcidin levels result in iron restriction and signs of anemia of chronic inflammation, although hepcidin-independent mechanisms contribute to development of anemia in HL.
Lingua originaleEnglish
pagine (da-a)2538-2543
Numero di pagine6
RivistaJournal of Clinical Oncology
Volume28
Stato di pubblicazionePubblicato - 2010

Keywords

  • Anemia
  • Hodgkin lymphoma
  • hepcidin

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