Anemia in Hodgkin's Lymphoma: The Role of Interleukin-6 and Hepcidin

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

doi:10.1200/jco.2009.27.6873

Cited by 96 publications

(66 citation statements)

References 41 publications

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“…However, in this study increased hepcidin concentrations appeared insufficient for the development of anemia (195 ), suggesting that compensation by increased erythropoiesis through increased EPO production may explain the lack of anemia in cancer despite increased hepcidin concentrations (196 ).…”

Section: Hepcidin In Cancercontrasting

confidence: 52%

Hepcidin in Human Iron Disorders: Diagnostic Implications

et al. 2011

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BACKGROUND:The peptide hormone hepcidin plays a central role in regulating dietary iron absorption and body iron distribution. Many human diseases are associated with alterations in hepcidin concentrations. The measurement of hepcidin in biological fluids is therefore a promising tool in the diagnosis and management of medical conditions in which iron metabolism is affected.CONTENT: We describe hepcidin structure, kinetics, function, and regulation. We moreover explore the therapeutic potential for modulating hepcidin expression and the diagnostic potential for hepcidin measurements in clinical practice.

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Section: Hepcidin In Cancercontrasting

confidence: 52%

Hepcidin in Human Iron Disorders: Diagnostic Implications

et al. 2011

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“…Among the cytokines that stimulate hepcidin synthesis, IL-6 26,84,85 and BMP-2 86 may be of particular clinical importance. Increased serum hepcidin concentrations have been found in acute infections, malaria, 87 inflammatory diseases, 27,88 multiple myeloma, 86 Hodgkin disease, 89 Castleman disease, 85 and in a subset of patients with solid tumors. 88,90 It is notable that in the IRIDA syndrome, relatively mild increases in hepcidin concentration are sufficient to sustain an iron-restricted anemia, even with parenteral iron supplementation (T.G., unpublished data, May 2010).…”

Section: Anemia Of Inflammationmentioning

confidence: 99%

Hepcidin and iron regulation, 10 years later

Ganz

2011

Blood

812

773

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Under evolutionary pressure to counter the toxicity of iron and to maintain adequate iron supply for hemoglobin synthesis and essential metabolic functions, humans and other vertebrates have effective mechanisms to conserve iron and to regulate its concentration, storage, and distribution in tissues. The iron-regulatory hormone hepcidin, first described 10 years ago, and its receptor and iron channel ferroportin control the dietary absorption, storage, and tissue distribution of iron. Hepcidin causes ferroportin internalization and degradation, thereby decreasing iron transfer into blood plasma from the duodenum, from macrophages involved in recycling senescent erythrocytes, and from iron-storing hepatocytes. Hepcidin is feedback regulated by iron concentrations in plasma and the liver and by erythropoietic demand for iron. Genetic malfunctions affecting the hepcidinferroportin axis are a main cause of iron overload disorders but can also cause iron-restricted anemias. Modulation of hepcidin and ferroportin expression during infection and inflammation couples iron metabolism to host defense and decreases iron availability to invading pathogens. This response also restricts the iron supply to erythropoietic precursors and may cause or contribute to the anemia associated with infections and inflammatory disorders. IntroductionThis review, occasioned by the 10th anniversary of the first publications on hepcidin, 1-4 focuses on the central role of hepcidin and its receptor/iron exporter ferroportin in the regulation of iron absorption, recycling, and tissue distribution in health and disease. A complementary overview of iron pathobiology was published in this journal 2 years ago. 5 Brief historyAlready in the 1930s, McCance and Widdowson estimated intestinal iron absorption by subtracting the iron content of feces and urine from the iron content of the diet (for references before year 2000, see the supplemental Appendix, available on the Blood Web site; see the Supplemental Materials link at the top of the online article). They noted that iron absorption was increased in irondeficient subjects. There was no change in iron excretion when already replete subjects were given parenteral iron, indicating that excretion was not regulated. Hahn and Whipple analyzed the kinetics of intestinal radioiron absorption and utilization in humans and animal models and confirmed that absorption was regulated and there was no significant excretion of iron. In the 1950s, Finch and Saylor established that iron absorption was also stimulated by increased erythropoietic activity and was suppressed by hypertransfusion. The recycling of hemoglobin from damaged radioironlabeled erythrocytes into iron was measured by Noyes, Bothwell, and Finch. More iron was released from the reticuloendothelial system when patients or experimental animals were iron-deficient, indicating that the release of iron from macrophages was regulated by iron stores. Freireich, Wintrobe, Cartright, Finch, and others showed that inflammation induced the sequestration...

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“…IL-6 is a potent inducer of hepcidin, a liver-produced iron regulatory hormone implicated in anemia of lymphoma, multiple myeloma, and Castleman disease (25)(26)(27). Siltuximab treatment has been associated with hemoglobin increases and hepcidin decreases in patients with renal cancer in an earlier clinical study (28).…”

Section: Pharmacodynamicsmentioning

confidence: 99%