Changes in disease activity, cytokine production, and proliferation of peripheral blood mononuclear cells in patients with rheumatoid arthritis after simvastatin treatment.
OBJECTIVE
The aim of this study was to investigate changes in disease activity, cytokine profiles, and proliferation of peripheral blood mononuclear cells (PBMCs) in active rheumatoid arthritis (RA) patients treated with simvastatin.


METHODS
Thirty-three patients with active RA were prescribed simvastatin (40 mg/day) for 3 months. Most of the patients received background traditional disease-modifying anti-rheumatic drugs (DMARDs) in stable doses. At the end of treatment there was a reduction in the 28-joint Disease Activity Score (DAS28) and in the Health Assessment Questionnaire (HAQ) score.


RESULTS
Eleven patients (33%) achieved a moderate European League Against Rheumatism (EULAR) response. There was a decrease in circulating interleukin (IL)-17 concentrations and spontaneous PBMC proliferation. Anti-CD3-stimulated IL-10 and tumour necrosis factor (TNF)alpha production by PBMCs was upregulated after simvastatin therapy. A reduction in serum IL-6 was detected only in the responder group. Baseline circulating IL-10 concentrations were higher in responders than in non-responders.


CONCLUSIONS
Simvastatin treatment is associated with moderate clinical improvement in patients with active RA. Immunological changes produced by simvastatin in peripheral blood are complex and may reflect both its anti- and pro-inflammatory properties.
Shirinsky
I V
IV
Department of Immunopharmacology, Institute of Clinical Immunology RAMS, Novosibirsk, Russia. ishirinsky@mail.ru
Zheltova
O I
OI
Solovyova
N Y
NY
Kozlov
V A
VA
Shirinsky
V S
VS
D000368:Aged; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004185:Disability Evaluation; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D020381:Interleukin-17; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D019821:Simvastatin