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Blood, 15 November 2005, Vol. 106, No. 10, pp. 3483-3489. Prepublished online as a Blood First Edition Paper on July 14, 2005; DOI 10.1182/blood-2005-05-1980. This Article Full Text (PDF) All Versions of this Article: 2005-05-1980v1 106/10/3483    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Mazodier, K. Articles by Kaplanski, G. Search for Related Content PubMed PubMed Citation Articles by Mazodier, K. Articles by Kaplanski, G. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 17, 2005 Accepted July 10, 2005 Severe imbalance of IL-18/IL-18BP in patients with secondary hemophagocytic syndrome Karin Mazodier, Valerie Marin, Daniela Novick, Catherine Farnarier, Stephane Robitail, Nicolas Schleinitz, Veronique Veit, Pascale Paul, Menachem Rubinstein, Charles A Dinarello, Jean-Robert Harle, and Gilles Kaplanski* Service de Medecine Interne, Hopital de la Conception, Marseille, France INSERM UMR600, Hopital Sainte-Marguerite, Marseille, France Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel Departement d' Informatique Medicale, Hopital Sainte-Marguerite, Marseille, France Laboratoire d' Exploration des NK, Laboratoire d' Hematologie, Hopital de la Conception, Marseille, France Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver, USA Service de Medecine Interne, Hopital de la Conception, Marseille, France; INSERM UMR600, Hopital Sainte-Marguerite, Marseille, France * Corresponding author; email: gilles.kaplanski{at}ap-hm.fr. Hemophagocytic syndrome (HPS) is characterized by an uncontrolled and poorly understood activation of Th-1 lymphocytes and macrophages. We studied 20 patients with HPS secondary to infections, autoimmune disease, lymphoma, or cancer and observed that the concentrations of serum IL-18, a strong inducer of Th-1 responses, IFN- production, stimulation of macrophages and NK cells was highly increased in HPS but not in control patients. In contrast, concentrations of its natural inhibitor, the IL-18 binding protein, were only moderately elevated, resulting in a high level of biologically active free IL-18 in HPS (4.6 fold increase compared with controls, P< 0.001). Free IL-18 but not IL-12 concentrations significantly correlated with clinical status and the biological markers of HPS such as anemia (P< 0.001), hypertriglyceridemia and hyperferritinemia (P<0.01), and also with markers of Th-1 lymphocyte or macrophage activation such as elevated concentrations of IFN-, soluble IL-2 and TNF receptors concentrations. Despite high IL-18 elevation, in vitro NK cell cytotoxicity was severely impaired in HPS patients, in part due to NK cell lymphopenia which was observed in a majority of patients, but also secondary to an intrinsic NK cell functional deficiency. We concluded that a severe IL-18/IL-18BP imbalance results in Th-1 lymphocyte and macrophage activation which escape control by NK cell cytotoxicity and may allow for secondary HPS in patients with underlying diseases. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Wang, J. Tan, Y. Wang, K. K. Meldrum, C. A. Dinarello, and D. R. Meldrum IL-18 binding protein-expressing mesenchymal stem cells improve myocardial protection after ischemia or infarction PNAS, October 13, 2009; 106(41): 17499 - 17504. [Abstract] [Full Text] [PDF] C. A. Nold-Petry, M. F. Nold, J. W. Nielsen, A. Bustamante, J. A. Zepp, K. A. Storm, J.-W. Hong, S.-H. Kim, and C. A. Dinarello Increased Cytokine Production in Interleukin-18 Receptor {alpha}-deficient Cells Is Associated with Dysregulation of Suppressors of Cytokine Signaling J. Biol. Chem., September 18, 2009; 284(38): 25900 - 25911. [Abstract] [Full Text] [PDF] C. Ponticelli and O. D. C. Alberighi Haemophagocytic syndrome--a life-threatening complication of renal transplantation Nephrol. Dial. Transplant., September 1, 2009; 24(9): 2623 - 2627. [Full Text] [PDF] A. Iannello, S. Samarani, O. Debbeche, R. Ahmad, M.-R. Boulassel, C. Tremblay, E. Toma, J.-P. Routy, and A. Ahmad Potential Role of Interleukin-18 in the Immunopathogenesis of AIDS: Involvement in Fratricidal Killing of NK Cells J. Virol., June 15, 2009; 83(12): 5999 - 6010. [Abstract] [Full Text] [PDF] A. Zirlik, S. M. Abdullah, N. Gerdes, L. MacFarlane, U. Schonbeck, A. Khera, D. K. McGuire, G. L. Vega, S. Grundy, P. Libby, et al. Interleukin-18, the Metabolic Syndrome, and Subclinical Atherosclerosis: Results From the Dallas Heart Study Arterioscler Thromb Vasc Biol, September 1, 2007; 27(9): 2043 - 2049. [Abstract] [Full Text] [PDF]

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