Jan 2, 2003
University of California, San Francisco, neurologists have demonstrated in mice that oral atorvastatin was able to prevent or reverse chronic and relapsing paralysis.
"Atorvastatin (Lipitor) was tested in chronic and relapsing experimental autoimmune encephalomyelitis, a CD4+ Th1-mediated central nervous system (CNS) demyelinating disease model of multiple sclerosis," wrote S. Youssef and colleagues in the journal Nature.
"Atorvastatin induced STAT6 phosphorylation and secretion of Th2 cytokines (interleukin (IL)-4, IL-5, and IL-10) and transforming growth factor (TGF)-beta. Conversely, STAT4 phosphorylation was inhibited and secretion of Th1 cytokines (IL-2, IL-12, interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha) was suppressed," reported the researchers.
"Atorvastatin promoted differentiation of Th0 cells into Th2 cells," they noted. "In adoptive transfer, these Th2 cells protected recipient mice from EAE induction."
Youssef's group also found that the drug "reduced CNS infiltration and major histocompatibility complex (MHC) class II expression. Treatment of microglia inhibited IFN-gamma-inducible transcription at multiple MHC class II transactivator (CIITA) promoters and suppressed class II upregulation. Atorvastatin suppressed IFN-gamma-inducible expression of CD40, CD80, and CD86 co-stimulatory molecules."
"L-Mevalonate, the product of HMG-CoA reductase, reversed atorvastatin's effects on antigen-presenting cells (APC) and T cells. Atorvastatin treatment of either APC or T cells suppressed antigen-specific T-cell activation. Thus, atorvastatin has pleiotropic immunomodulatory effects involving both APC and T-cell compartments," the neurologists wrote (The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Nature, 2002;420(6911):78-84).
They concluded that "[s]tatins may be beneficial for multiple sclerosis and other Th1-mediated autoimmune diseases."
The contact person for this report is S.S. Zamvil, University California San Francisco, Department Neurology, 521 Parnassus Avenue, San Francisco, CA 94143, USA.
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The information in this article comes under the major subject areas
of Autoimmune Disease, Central Nervous System Disease, Paralysis, Statins,
Animal Models. This article was prepared by Drug Week editors from staff
and other reports.
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