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Arsenic trioxide: A promising novel therapeutic agent for lymphoproliferative and autoimmune syndromes in MRL/lpr mice. | LitMetric

AI Article Synopsis

  • MRL/lpr mice exhibit a lupus-like syndrome due to the failure of apoptosis, similar to autoimmune lymphoproliferative syndrome (ALPS), and there's currently no effective treatment available for ALPS.
  • Arsenic trioxide (As2O3) significantly reduces antibody and cell-mediated symptoms in these mice, activating caspases that eliminate excessive T lymphocytes and improve survival rates.
  • The treatment also lowers levels of various harmful immune substances and restores crucial antioxidant levels, showing potential as a new therapy for autoimmune diseases.

Article Abstract

MRL/lpr mice develop a human lupuslike 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-gamma, nitric oxide metabolite, TNF-alpha, 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.

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Source
http://dx.doi.org/10.1182/blood-2006-04-020610DOI Listing

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