EFFECTS OF STATINS UPON ANTIGEN-SPECIFIC LYMPHOCYTE ACTIVATION IN PATIENTS WITH RHEUMATOID ARTHRITIS: AN IN VITRO STUDY

Abstract

Abstract. Collagen type II (Col II) is among the proposed candidate autoantigens initiaiting rheumatoid arthritis (RA). Statins have been shown to have anti-inflammatory and immunomodulating properties. Mechanisms of statin effects upon the autoantigen-induced T lymphocyte activation in RA patients are still unknown. The aim of present study was to evaluate the effects of mevastatin upon Col II- and anti-CD3-induced (PBMC) activation of peripheral blood mononuclear cells (PBMC) from RA patients. PBMC from active RA patients (DAS28 – 6.6±0.64) were stimulated with antibodies specific for either anti-CD3 or anti-Col II. The cultured cells were treated with mevastatin at different concentrations. Mevalonic acid, geranylgeranyl pyrophosphate (GGpp) and farnesyl pyrophosphate (Fpp) were added to cultures. Mevastatin at concentration of 10 μM caused significant reduction of Col II-induced PBMC proliferation and of IFNγ production. These mevastatin effects were partially reversible by addition of mevalonic acid, GGpp, and Fpp. Mevastatin did not influence the anti-CD3 induced PBMC activation. In conclusion, mevastatin is able to suppress antigen-specific T-cell stimulation in RA patients, due to decreased production of mevalonic acid metabolites.

Keywords

• rheumatoid arthritis
• statins
• in vitro