Statins as immunomodulators: comparison with interferon-beta 1b in MS.
BACKGROUND
Recent data suggest that statins may be potent immunomodulatory agents. In order to evaluate the potential role of statins as immunomodulators in MS, the authors studied their immunologic effects in vitro and compared them to interferon (IFN)beta-1b.


METHODS
Peripheral blood mononuclear cells (PBMC) obtained from untreated or IFN beta-1-treated patients with relapsing-remitting MS or from healthy donors (HD) 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. The authors analyzed proliferative activity of T cells 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.


RESULTS
All three statins inhibited proliferation of stimulated PBMC in a dose-dependent manner, with simvastatin being the most potent, followed by lovastatin and mevastatin. IFN beta-1b showed a similar effect; statins and IFN beta-1b together added their inhibitory potentials. Furthermore, statins 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. Besides strong anti-inflammatory properties, statins also exhibited some proinflammatory effects.


CONCLUSIONS
Statins are effective immunomodulators in vitro that merit evaluation as treatment for MS.
Neuhaus
O
O
Department of Neurology, Multiple Sclerosis Research Group, Karl-Franzens-Universität, Graz, Austria.
Strasser-Fuchs
S
S
Fazekas
F
F
Kieseier
B C
BC
Niederwieser
G
G
Hartung
H P
HP
Archelos
J J
JJ
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000494:pharmacology / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology; D019707:Receptors, Chemokine / Q000276:immunology / Q000378:metabolism; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D000276:Adjuvants, Immunologic; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019707:Receptors, Chemokine; D000068576:Interferon beta-1b; D016899:Interferon-beta; D000068556:Interferon beta-1a