ORIGINAL ARTICLE

Effects of low-dosage simvastatin on rheumatoid arthritis through reduction of Th1/Th2 and CD4/CD8 ratios

Authors

Hiroko Kanda¹, Kazuhiro Yokota², Chieko Kohno², Tetsuji Sawada¹, Kojiro Sato³, Masao Yamaguchi¹, Yoshinori Komagata¹, Kota Shimada⁴, Kazuhiko Yamamoto¹ and Toshihide Mimura²

1. Department of Allergy and Rheumatology, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
2. Division of Rheumatology and Applied Immunology, Department of Medicine, Saitama Medical University, Saitama, Japan
3. Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
4. Department of Rheumatology, Sagamihara National Hospital, National Hospital Organization, Kanagawa, Japan

Received:

09 January 2007

Accepted:

07 May 2007

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Abstract

The objective of this study was to assess both the anti-inflammatory and immunomodulatory effects of low-dosage simvastatin on rheumatoid arthritis (RA). In each patient, simvastatin at 10mg/day was administered for 12 weeks. The other treatments were unchanged at least 3 months before simvastatin administration to the end of the study. Patients were assessed for the improvement in clinical, laboratory, and immunological parameters of RA and for adverse events. Twenty-four patients with RA were enrolled. Clinical symptoms, including patient's assessment of pain and disease activity on visual analog scale (VAS), the swollen joint and tender joint counts, and handgrip strength significantly improved. Physician's assessment of disease activity on VAS, a period of morning stiffness and modified health assessment questionnaire showed a tendency of improving after administration of low-dosage of simvastatin. Of special interest was that the median levels of erythrocytes sedimentation rate, C-reactive protein, and rheumatoid factor were significantly decreased from 54.0mm/h to 45.5mm/h, from 1.50mg/dl to 0.85mg/dl, and from 57.0IU/ml to 28.0IU/ml, respectively, after administration of simvastatin. ACR20 and ACR50 responses were achieved in 62% and 38%, respectively, of simvastatin-treated patients for 12 weeks. Immunological assessment in peripheral blood revealed that the Th1/Th2 and CD4/CD8 ratios were significantly reduced by simvastatin. No adverse events were reported during simvastatin treatment. Immunomodulation through the alteration of Th1/Th2 and CD4/CD8 ratios may be a pharmacological mechanism in the anti-rheumatic effect of low-dosage simvastatin. Although it is necessary to evaluate the long-term effects of statins, low-dosage statins appear to be good as additional therapeutic agents.

Key words

CD4/CD8 - Inflammatory - Rheumatoid arthritis - Simvastatin - Statin - Th1/Th2