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Blood, 1 April 2008, Vol. 111, No. 7, pp. 3902-3903. This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Weiss, G. Articles by Theurl, I. Search for Related Content PubMed Articles by Weiss, G. Articles by Theurl, I. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CORRESPONDENCE Response: Monocyte hepcidin and the anemia of chronic disease We appreciate the comments of our colleagues and agree with them that conditional knockouts of hepatocytes would be a pivotal tool to provide us with new information on the true role of monocyte-derived hepcidin for the control of body iron homeostasis under inflammatory conditions. An alternative approach would be to study this issue by functional knockout of monocytes using clodronate liposomes. However, it has to be kept in mind that the amount of hepcidin produced by monocytes/macrophages is a magnitude lower than that reported for hepatocytes.1 Thus, due to its low concentration, systemic effects on iron absorption as observed in transgenic or hepcidin knockout mice are unlikely to be exerted by monocyte-derived hepcidin.2,3 Accordingly, the presumed function of monocyte hepcidin is to readily control ferroportin-mediated iron release by monocytes in an autocrine fashion, especially at sites of poor perfusion where circulatory hepcidin is not abundant. This may be part of a defense strategy of the body to limit iron availability for extracellular pathogens. In addition, cytokines produced by activated monocytes/macrophages such as interleukin (IL)-1β and IL-6 may further stimulate local formation of this peptide. Further, our colleagues questioned why circulating ferritin levels were not correlated with hepcidin mRNA levels determined in monocytes of patients with anemia of chronic disease (ACD).4 Circulating ferritin concentrations under inflammatory conditions are the reflection of iron overload, the regulatory effects of cytokines on ferritin expression, and cellular apoptosis. Importantly, in contrast to hepcidin expression in the liver, this gene cannot be induced in monocytes or macrophages upon iron challenge,1,4 which partly explains the lack of correlation. In addition, cytokines, which are known to strongly induce ferritin expression such as tumor necrosis factor-alpha, negatively affect hepcidin formation at least in hepatocytes.5 Whether this also applies to hepcidin induction of monocytes has to be shown. Animal models of anemia of chronic disease together with tissue-specific elimination of hepcidin and/or its regulatory molecules will be essential tools for acquiring deeper insights into the multiple roles of this small antimicrobial peptide during inflammatory processes.    Authorship Top Authorship References   Conflict-of-interest disclosure: The authors declare no competing financial interests. Correspondence: Guenter Weiss, Medical University, Department of General Internal Medicine, Anichstrasse 35, A-6020 Innsbruck, Austria 6020; e-mail: guenter.weiss{at}i-med.ac.at. Guenter Weiss, and Igor Theurl    References Top Authorship References   Peyssonnaux C, Zinkernagel AS, Datta V, Lauth X, Johnson RS, Nizet V. TLR4-dependent hepcidin expression by myeloid cells in response to bacterial pathogens. Blood 2006; 107:3727–3732.[Abstract/Free Full Text] Nicolas G, Bennoun M, Devaux I, et al. Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice. Proc Natl Acad Sci U S A 2001; 98:8780–8785.[Abstract/Free Full Text] Roy CN, Mak HH, Akpan I, Losyev G, Zurakowski D, Andrews NC. Hepcidin antimicrobial peptide transgenic mice exhibit features of the anemia of inflammation. Blood 2007; 109:4038–4044.[Abstract/Free Full Text] Theurl I, Theurl M, Seifert M, et al. Autocrine formation of hepcidin induces iron retention in human monocytes. Blood 2008; 111:2392–2399.[Abstract/Free Full Text] Nemeth E, Valore EV, Territo M, Schiller G, Lichtenstein A, Ganz T. Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein. Blood 2003; 101:2461–2463.[Abstract/Free Full Text] CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Elucidating the role of monocyte-derived hepcidin Harish P. Janardhan Blood 2008 111: 3902. [Full Text] [PDF] This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Weiss, G. Articles by Theurl, I. Search for Related Content PubMed Articles by Weiss, G. Articles by Theurl, I. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?

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