NHEThe HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease.
Youssef S, Stuve O, Patarroyo JC, Ruiz PJ, Radosevich JL, Hur EM, Bravo M, Mitchell DJ, Sobel RA, Steinman L, Zamvil SS.
Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University, Stanford, California 94305, USA.
Statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, which are approved for cholesterol reduction, may also be beneficial in the treatment of inflammatory diseases. 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. Here we show that oral atorvastatin prevented or reversed chronic and relapsing paralysis. 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 tumour necrosis factor (TNF)-alpha) was suppressed. Atorvastatin promoted differentiation of Th0 cells into Th2 cells. In adoptive transfer, these Th2 cells protected recipient mice from EAE induction. Atorvastatin 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. Statins may be beneficial for multiple sclerosis and other Th1-mediated autoimmune diseases.
Statin activity in treating MS
Statin activity in treating MS
Summary
For reasons that go beyond cholesterol reduction, the most widely used prescription drugs in the US are being explored as treatments for central nervous system disorders, including multiple sclerosis (MS) and Alzheimer’s disease. Statins exhibit a variety of immunomodulatory effects in MS, and so far, pilot trials have found them to be safe. In Alzheimer’s disease, epidemiologic findings linking statins to reduced risk of dementia remain controversial.
http://www.neura.net/images/pdf/Winter06Statins.pdf
When I met my neuro a few weeks ago I mentioned statins and he responded "they cause muscle damage". The UK MS Society is holding a conference this weekend and one of the presentations is about statins. I'll post the results but I suspect it will be "on the one hand... on the other hand...".
What is so frustrating is that therapies are identified which might help, such as statins, monocyline etc, then years go by and trials are in progress, but no-one ever comes up with a definitive answer - are they worth taking or not? This disease must be a researchers dream.
Ian
Lori
I truly believe in the benefit of Vit D and sunshine! In fact, we used to live in Columbus, OH. We vacationed here in Naples often. After I was dxd I found that I felt better here. So we decided to make it permanant and moved here. I am sure that the sunshine helps tremendously (even if it is just in my mind!) It doesnt' really matter, does it, as long as it works?! Let me know if you vacation here again.
Lori
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Statins
Any feedback from the UK MS Conference regarding the use of statins?
It would seem encouraging that this treatment is being discussed at such a conference and also that particular neuros are now prescribing statins, albeit in conjunction with the interferons/copaxone.
Thanks & regards,
Phil.
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