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

Abstract

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 infl ammatory 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 signifi cantly decreased compared with that of control subjects. AT signifi cantly reduced erythrosedimentation, C-reactive protein, and disease activity. Concomitantly, T reg numbers and suppressive functions were signifi cantly 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. In conclusion, AT signifi cantly increased T reg numbers and restored their suppressive function in the RA patients, and this may be relevant in the modulation of uncontrolled infl ammation in this disorder. Copyright © 2011 by the American Society for Biochemistry and Molecular Biology, Inc.