Atorvastatin upregulates regulatory T cells and reduces clinical disease activity in patients with rheumatoid arthritis

Abstract

In this study, we investigated the hypothesis that regulatory T cells (T-reg) are involved in the immunomodulatory effects of statins on rheumatoid arthritis (RA) patients. The 12-week study cohort consisted of 55 RA patients and 42 control subjects allocated to either a group treated with atorvastatin (AT) (20 mg/day) or a non-AT group. T-reg numbers, suppressive function, serum inflammatory markers, and disease activity were evaluated before and after the therapy. Furthermore, the effects of AT on the frequency and suppressive function of T-reg were determined in vitro. Our data revealed that the suppressive function of T-reg from RA patients significantly decreased compared with that of control subjects. AT significantly reduced erythrosedimentation, C-reactive protein, and disease activity. Concomitantly, T-reg numbers and suppressive functions were significantly improved by AT. Consistent with the in vivo experiments, AT promoted the generation of T-reg from primary T cells and enhanced preexisting T-reg function in vitro. Moreover, we showed that PI3K-Akt-mTOR and ERK signal pathways were involved in the induction of T-reg by AT.jlr In conclusion, AT significantly increased T-reg numbers and restored their suppressive function in the RA patients, and this may be relevant in the modulation of uncontrolled inflammation in this disorder.-Tang, T-T., Y. Song, Y-J. Ding, Y-H. Liao, X. Yu, R. Du, H. Xiao, J. Yuan, Z-H. Zhou, M-Y. Liao, R. Yao, H. Jevallee, G-P. Shi, and X. Cheng. Atorvastatin upregulates regulatory T cells and reduces clinical disease activity in patients with rheumatoid arthritis. J. Lipid Res. 2011. 52: 1023-1032