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Common cholesterol drug prevents, reverses MS symptoms in mice

Federation of American Societies for Experimental Biology

Lipitor ™ (atorvastatin), the most frequently used cholesterol lowering agent in the world, also has the ability to influence the immune system and proved effective in reversing paralysis in a mouse model of multiple sclerosis. Dr. Sawsan Youssef, a postdoctoral fellow in the laboratory of Dr. Lawrence Steinman, Stanford University, reported the study on April 23 at the Experimental Biology 2002 meeting in New Orleans.

Multiple sclerosis is caused by the immune system attacking the body's own central nervous system, breaking down the myelin that sheathes and protects CNS nerves, impairing the body's ability to move normally, and eventually causing paralysis. The T lymphocytes of the mice with which the research team worked are sensitized to brain antigens so that they produce an over-abundance of cytokines, pro-inflammatory chemicals that inflame the CNS, causing demylination of nerve sheaths through the same mechanism and in the same manner as happens in human multiple sclerosis. As in humans with MS, this mouse condition (called experimental autoimmune encephalomyelitis or EAE) can occur in either an acute or relapsing form. The researchers found that oral treatment with lipitor could prevent both the acute and relapsing form of the multiple sclerosis-like disease in the mice, and could also reverse symptoms in mice with the ongoing chronic relapsing form of the disease. Compared with control mice, the mice treated with lipitor had much less CNS inflammation. A close comparison of the lymphocytes of lipitor-treated and control-treated mice showed that lipitor prevented the induction of the pro-inflammatory cytokines and induced secretion of anti-inflammatory cytokines.

Dr. Youssef says that the mechanism by which lipitor affected the immune system suggests that it and other statin medications may have implications for the treatment of multiple sclerosis and other inflammatory autoimmune diseases including insulin-dependent diabetes mellitus and rheumatoid arthritis.

Dr. Youssef and Dr. Steinman are working closely on this study with Dr. Scott Zamvil, University of California at San Francisco. Other members of the research team for this paper are Dr. Pedro Ruiz, Stanford, and Dr. Olaf Stuve, UCLA.


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