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J Clin Oncol. 2010 May 20;28(15):2538-43. doi: 10.1200/JCO.2009.27.6873. Epub 2010 Apr 20.

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

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  • 1Institute of Hematology, Catholic University S. Cuore, Rome, Italy. stefan.hohaus@rm.unicatt.it

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.

PMID:
20406921
DOI:
10.1200/JCO.2009.27.6873
[PubMed - indexed for MEDLINE]
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