Anti-inflammatory effects of atorvastatin on peripheral blood mononuclear cells and synovial fibroblasts in rheumatoid arthritis

作者：Blaschke S^*; Viereck V; Schwarz G; Klinger H M; Guerluek S; Mueller G A

来源：Scandinavian Journal of Rheumatology, 2009, 38(4): 235-239.

DOI：10.1080/03009740802572475

Objective: Statins, such as atorvastatin (ATV), are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors known to exert lipid-lowering but also anti-inflammatory, effects. In this study, we analysed the in vitro effects of ATV on peripheral blood mononuclear cells (PBMCs) and fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA), a chronic inflammatory joint disease.
Methods: PBMCs isolated from 25 RA patients and 20 healthy blood donors were stimulated in vitro with 0.1 mu M ATV for 24 h. PBMC cultures were analysed for cell surface markers to characterize T-cell subtypes (CD4, CD8, CD69, HLA-DR) by flow cytometry and for T helper cell type 1 (Th1) and type 2 (Th2) cytokines [interferon-gamma (IFN-gamma), interleukin-4 (IL-4), IL-10] in culture supernatants by enzyme-linked immunosorbent assay (ELISA). Furthermore, RNA isolated from ATV-stimulated RA-FLS pre- and post-ATV stimulation was analysed by microarray and quantitative reverse transcription polymerase chain reaction (RT-PCR).
Results: Flow cytometric analysis of T-cell subsets revealed no significant differences for CD4, CD8, CD69, and HLA-DR surface marker expression of PBMCs in RA patients and healthy controls after ATV stimulation. However, the proportion of IFN-gamma expressing CD4( ) T cells and the IFN-gamma cytokine concentrations in culture supernatants were significantly reduced in T-cell cultures from RA patients. In ATV-stimulated FLS a significant downregulation of proinflammatory cytokine (IL-6) and chemokine (IL-8) expression was detected (p < 0.001).
Conclusions: Our study demonstrates a marked in vitro anti-inflammatory activity of ATV in RA including a systemic effect on a pathogenic CD4( ) T-cell population (Th1) and a local effect on FLS. These findings may provide a scientific rationale for statins as add-on therapy in RA.

• 出版日期2009