Immune regulation of inflammatory arthritis by a natural product resveratrol

QR180 Immunology;RM Therapeutics. Pharmacology

Gao, Xiuzhu ; Xu, Damo

University:University of Glasgow

Department:Institute of Infection Immunity and Inflammation

关键词: Inflammatory arthritis, resveratrol, immune;   

Others  :  http://theses.gla.ac.uk/2361/1/2011GaoMSc.pdf

来源: University of Glasgow

【 摘 要 】

Rheumatoid arthritis (RA) is one of the most common chronic diseases worldwide. It is characterised by inflammatory cell infiltration and bone erosion. Current therapy using non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids are not very effective and can have severe side effects. New generation recombinant drugs while effective are costly. Thus, better therapeutic strategies are critically needed. Natural products with fewer side effects and which are less expensive may represent ideal drugs for clinical RA. Resveratrol is a phytoalexin mainly derived from the skin of red grapes. Many in vitro and in vivo studies have demonstrated that resveratrol has a wide-range of anti-oxidant, anti-proliferative and anti-inflammatory properties. The aim of this project was to establish whether resveratrol has an effect on the development and pathogenesis of inflammatory arthritis.Collagen induced arthritis (CIA) is a well-studied animal model for human rheumatoid arthritis was used here to study the role of resveratrol in RA.It was first determined whether resveratrol could prevent CIA. CIA mice were administered with different doses of resveratrol before the onset of arthritis. It was found that 20mg/kg but not 15 mg/kg of resveratrol reduced CIA clinical parameters and severity of joint histology respectively. Second effect of resveratrol on established CIA was investigated and there was evidence that resveratrol, when given after the onset of CIA, could effectively suppress the progress and severity of CIA. The clinical anti-arthritic effect of resveratrol was accompanied by the reduction of collagen-specific antibodies in CIA mice. Additionally, resveratrol treatment also dramatically reduced the levels of inflammatory cytokines, in particular, IL-17, IFN-g and TNF-a in the serum. The number of T lymphcytes was also reduced, in particular the IL-17 and IFN-g expressing CD4+T cells in DLN.The results therefore demonstrate that resveratrol has the property to prevent and treat inflammatory arthritis by modulating the key auto-antigen-specific antibody and T cell responses. Thus, resveratrol, a natural product may have the potential to be used as a novel drug for arthritis.