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Blood, 15 December 2006, Vol. 108, No. 13, pp. 3967-3975. Prepublished online as a Blood First Edition Paper on August 22, 2006; DOI 10.1182/blood-2006-04-020610. This Article Full Text (PDF) All Versions of this Article: blood-2006-04-020610v1 108/13/3967    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 Bobe, P. Articles by Chelbi-Alix, M. K Search for Related Content PubMed PubMed Citation Articles by Bobe, P. Articles by Chelbi-Alix, M. K Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 28, 2006 Accepted August 2, 2006 Arsenic trioxide, a novel promising therapeutic agent for lymphoproliferative and autoimmune syndromes in MRL/lpr mice Pierre Bobe, Danielle Bonardelle, Karim Benihoud, Paule Opolon, and Mounira K Chelbi-Alix* CNRS UPR 9045, 7, rue Guy-Moquet, 94801 Villejuif Cedex, France CNRS/Institut Gustave-Roussy, UMR 8121, rue Camille-Desmoulins, Villejuif Cedex, France * Corresponding author; email: mchelbi{at}vjf.cnrs.fr. MRL/lpr mice develop a human-lupus-like syndrome and, as in autoimmune lymphoproliferative syndrome (ALPS), massive lymphoproliferation due to inactivation of Fas-mediated apoptosis. Presently, no effective therapy exists for ALPS, and long term, therapies for lupus are hazardous. We show herein that arsenic trioxide (As2O3) is able to achieve quasi-total regression of antibody- and cell-mediated manifestations in MRL/lpr mice. As2O3 activated caspases, and eliminated the activated T lymphocytes responsible for lymphoproliferation, and skin, lung and kidney lesions, leading to significantly prolonged survival rates. This treatment also markedly reduced anti-DNA autoantibody, rheumatoid factor, IL-18, IFN-, nitric oxide metabolite, tumor necrosis factor-, Fas-ligand and IL-10 levels, and immune-complex deposits in glomeruli. As2O3 restored cellular reduced glutathione levels, thereby limiting the toxic effect of nitric oxide, which is overproduced in MRL/lpr mice. Furthermore, As2O3 protected young animals against developing the syndrome and induced almost total disease disappearance in older affected mice, thereby demonstrating that it is a novel promising therapeutic agent for autoimmune diseases. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Poisoning autoimmunity Vito Pistoia Blood 2006 108: 3964-3965. [Full Text] [PDF] This article has been cited by other articles: T. B. Sundberg, L. Swenson, D. R. Wahl, A. W. Opipari Jr., and G. D. Glick Apoptotic Signaling Activated by Modulation of the F0F1-ATPase: Implications for Selective Killing of Autoimmune Lymphocytes J. Pharmacol. Exp. Ther., November 1, 2009; 331(2): 437 - 444. [Abstract] [Full Text] [PDF] D. T. Teachey, A. E. Seif, V. I. Brown, M. Bruno, R. M. Bunte, Y. J. Chang, J. K. Choi, J. D. Fish, J. Hall, G. S. Reid, et al. Targeting Notch signaling in autoimmune and lymphoproliferative disease Blood, January 15, 2008; 111(2): 705 - 714. [Abstract] [Full Text] [PDF] Arsenic Trioxide for Autoimmune Diseases? Journal Watch Oncology and Hematology, January 12, 2007; 2007(112): 5 - 5. [Full Text]

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