Immunomodulatory effects of 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors, potential therapy for relapsing remitting multiple sclerosis.
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.
Peng
Xueyan
X
Department of Neurology, Yale University, 40 Temple St., New Haven, CT 06510, USA.
Jin
Jianping
J
Giri
Shailendra
S
Montes
Monica
M
Sujkowski
Danuta
D
Tang
Yunan
Y
Smrtka
Jennifer
J
Vollmer
Timothy
T
Singh
Inderjit
I
Markovic-Plese
Silva
S
D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D015151:Immunoblotting; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020825:T-Box Domain Proteins / Q000096:biosynthesis; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D000098815:T-bet Transcription Factor
D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor