Abstract
This study characterized immunomodulatory targets of statins in humans and their potential for treatment of relapsing remitting multiple sclerosis (RR MS). Statins inhibited the proliferative response of mononuclear cells. Simvastatin, the statin with the strongest antiproliferative effect, inhibited IFN-gamma-induced expression of MHC class II DR on monocytes and decreased their antigen presenting capacity. As for T lymphocytes, it inhibited their activation and expression of the Th1 lineage differentiation markers. Simvastatin inhibited IFN-gamma, TNF-alpha, and IL-2 secretion, as well as the expression of T-bet, a transcription factor that regulates Th1 cell differentiation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Differentiation / drug effects
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Cell Differentiation / immunology
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Cells, Cultured
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Cytokines / biosynthesis
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Cytokines / drug effects
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Flow Cytometry
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Histocompatibility Antigens Class II / biosynthesis
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Histocompatibility Antigens Class II / drug effects
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Humans
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Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
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Immunoblotting
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Lymphocyte Activation / drug effects
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Lymphocyte Culture Test, Mixed
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Multiple Sclerosis, Relapsing-Remitting / drug therapy*
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Multiple Sclerosis, Relapsing-Remitting / immunology*
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Oligonucleotide Array Sequence Analysis
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Reverse Transcriptase Polymerase Chain Reaction
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T-Box Domain Proteins / biosynthesis
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T-bet Transcription Factor
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Th1 Cells / cytology
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Th1 Cells / drug effects*
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Th1 Cells / immunology
Substances
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Cytokines
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Histocompatibility Antigens Class II
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Hydroxymethylglutaryl-CoA Reductase Inhibitors
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T-Box Domain Proteins
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T-bet Transcription Factor