Oct 08, 2002
By Will Boggs, MD
Lipid-lowering statin drugs also have immunomodulatory properties that may prove useful in treating immune-mediated disorders, according to a report in the October 8th issue of Neurology.
Statins have been shown in cell culture and animal models to have potent immunomodulatory effects, the authors explain, suggesting they might benefit patients with disorders such as MS, rheumatoid arthritis or type 1 diabetes.
Dr. Juan J. Archelos from Karl-Franzens-Universitat in Graz, Austria and colleagues investigated the effects of various statins on the immune responses of peripheral blood mononuclear cells (PBMCs) and T cells drawn from 74 interferon-beta-1-treated MS patients and from 25 healthy donors.
Statins, most notably simvastatin, inhibited the proliferation of T cells in response to various stimuli, the authors report, without significantly altering the proliferation of resting T cells. The effects were similar in patients and controls.
This effect, which preferentially affected memory T cells, was comparable to that observed with interferon-beta-1b, the report indicates.
Statins also significantly reduced the expression of chemokine receptors on both T and B cells, the researchers note, and modified stimulation-induced expression of adhesion molecules on T cells (reducing ICAM-1 and increasing L-selectin expression to a greater extent than did interferon).
Moreover, simvastatin shifted the T helper 1/T helper 2 balance toward the Th1 profile (in other words, in a direction opposite that caused by interferon), the results indicate. Simvastatin also downregulated MMP-9, an enzyme implicated in the pathogenesis of MS.
"Lipid-lowering statins are potent immunomodulators, which extends their future putative use to all types of auto-immune-mediated disorders, such as MS, diabetes, rheumatoid arthritis, and rejection in organ transplantation, among others," Dr. Archelos told Reuters Health.
"It is an exciting possibility that oral drugs that are not systemically immunosuppressive could be beneficial in MS," write Dr. Scott S. Zamvil from University of California, San Francisco, and Dr. Lawrence Steinman from Stanford Medical School in Stanford, California in a related editorial. "The efficacy of statins should be tested in controlled clinical trials."
"A small-scale phase II clinical trial on MS is ongoing at the Medical University of South Carolina in collaboration with investigators at Yale University and at the University of Colorado Health Sciences Center," Dr. Archelos said. "The trial will last 2 years, and first results are expected at the end of 2003."
"To better understand the immunomodulatory effects of statins, these trials must be accompanied by further in vitro studies on the immune cells of these patients," Dr. Archelos concluded. "Further research on experimental animal models will help to elucidate which exact mechanisms are responsible for the immunomodulatory effects of statins."
© 2002 Reuters Ltd