Issue |
Med Sci (Paris)
Volume 24, Number 11, Novembre 2008
|
|
---|---|---|
Page(s) | 967 - 971 | |
Section | M/S revues | |
DOI | https://doi.org/10.1051/medsci/20082411967 | |
Published online | 15 November 2008 |
De nouvelles perspectives thérapeutiques pour l’arsenic
De la leucémie aiguë promyélocytaire aux maladies auto-immunes
New therapeutic perspectives for Arsenic: from acute promyelocytic leukemia to autoimmune diseases
CNRS FRE 2937, Institut André Lwoff, 7 rue Guy Moquet, 94801 Villejuif Cedex, France
*
bobe@infobiogen.fr
*
mchelbi@vjf.cnrs.fr
Le traitement depuis 1996 de la leucémie aiguë promyélocytaire par le trioxyde d’arsenic (As2O3) a ouvert la voie de son utilisation dans d’autres cancers. Fait nouveau, l’As2O3 permet aussi de traiter les syndromes auto-immuns et lymphoprolifératifs de la souris MRL/lpr en induisant l’apoptose des lymphocytes T activés responsables des atteintes cutanées, pulmonaires et rénales, et de la lymphoprolifération. L’As2O3 normalise les taux sériques de nombreuses cytokines (TNF-α, IL-18, IFN-γ, IL-10), de Fas ligand, et des métabolites du monoxyde d’azote. En inhibant la production d’auto-anticorps, il bloque le développement de la glomérulonéphrite, ce qui conduit à une augmentation spectaculaire de la durée de vie de la souris.
Abstract
Since 1996, arsenic trioxide (As2O3) is used to treat patients with acute promyelocytic leukemia. We have recently shown that As2O3 is a novel promising therapeutic agent for the autoimmune diseases (human lupus-like syndrome) and the massive lymphoproliferation (human autoimmune lymphoproliferative-like syndrome) developed by MRL/lpr mice. As2O3 is able to achieve an almost complete regression of antibody- and cell-mediated manifestations in MRL/lpr mice. As2O3 eliminated the activated T lymphocytes responsible for lymphoproliferation and skin, lung, and kidney lesions. This treatment also markedly reduced anti-DNA autoantibodies, rheumatoid factor, IL-18, IFN-γ, nitric oxide metabolites, TNF-α, Fas ligand and IL-10 levels, and immunecomplex deposits in glomeruli, leading to significantly prolonged survival rates.
© 2008 médecine/sciences - Inserm / SRMS
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