Ebosin: a potential therapeutic agent for rheumatoid arthritis and autoinflammatory syndromes

摘要

Rheumatoid arthritis(RA)is a chronic autoimmune disease that has a worldwide prevalence of 1%.The symptoms of RA are pain,stiffness and symmetrical synovitis of diarthrodial joints,which result in articular destruction,functional decline,and substantial comorbidity in the cardiovascular,neurologic and metabolic systems.1 In RA,fibroblast-like synoviocytes(FLS,Type B synoviocytes)and osteoclasts are the main cells that contribute to bone and cartilage degradation,respectively.2 Pro-inflammatory cytokines,including interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and IL-6,play an essential role in the activation of FLS and the differentiation of osteoclasts,which have been implicated in the pathogenesis of RA.3 Targeting pro-inflammation cytokines and blocking their signal pathways have become an important strategy in RA treatment.The major functions of TNF-αin RA are associated with the production of pro-inflammation cytokines,inflamed synovium,chemokine amplification,Treg cells and osteoclast recruitment.4 As a TNF inhibitor,etanercept5 is a human recombinant version of the soluble p75 TNF receptor that is linked to the Fc of human immunoglobulin G subclass 1(IgG1),and it acts as a competitive inhibitor of the binding of TNF-αto cell-surface TNF receptors and thereby inhibits TNF-α-induced pro-inflammatory activity in the joints of RA patients.