Medscape Neurology & Neurosurgery 4(2), 2002.
From Neurology October 8, 2002 (Volume 59, Number 7)
Neuhaus O, Strasser-Fuchs S, Fazekas F, et al.
Statin agents have been heralded for their ability to reduce cholesterol levels and the risk of cardio- and cerebrovascular events, but their role as immunomodulators may be just as potent. Neuhaus and colleagues conducted a study to assess the potential of statin agents as immunomodulators in multiple sclerosis (MS) by examining the immunologic effects of statins in vitro compared with interferon (IFN) beta-1b.
Blood was obtained from 74 patients with MS and 25 healthy donors. Of the 74 patients with MS, 60 had remitting-relapsing MS and 14 had secondary progressive MS. In total, 39 of those with MS were being treated with IFN beta-1a, 19 with IFN beta-1b, and 16 were not receiving immunotherapy. Peripheral blood mononuclear cells (PBMC) and T cells were stimulated with concanavalin A, phytohemagglutinin, or antibody to CD3 in the presence of lovastatin, simvastatin, mevastatin, IFN beta-1b, or statins plus IFN beta-1b. Testing was performed to analyze the proliferative activity of T and B cells, cytokine production and release, activity of matrix metalloproteinases (MMP), and surface expression of activation markers, adhesion molecules, and chemokine receptors on both T and B cells.
The results showed that all 3 statins inhibited proliferation of stimulated PBMC in a dose-dependent manner. Simvastatin (the least hydrophilic) was the most potent followed by lovastatin and mevastatin. Notably, the combination of IFN beta-1b and statins suppressed proliferation, further demonstrating their combined inhibitory potentials. Statins also reduced the expression of activation-induced adhesion molecules on T cells, modified the T helper 1/T helper 2 cytokine balance, reduced MMP-9, and downregulated chemokine receptors on both B and T cells. The results of the study support the notion of statins as immunomodulators and further investigation is required to determine their role in the treatment of MS.
Related Reports of Interest
immunomodulatory effects of interferon-beta in multiple sclerosis include
the upregulation of T helper 1-associated marker genes
Ann Neurol. 2001;50:349-357.
© 2002 Medscape