Paradoxical Effects of Adenovirus-Mediated Blockade of TNF Activity in Murine Collagen-Induced Arthritis

摘要: Collagen-induced arthritis (CIA) is an experimental model of widely used to dissect the pathogenesis human rheumatoid and identify potential therapeutic targets. Among these, TNF-α has been recognized play important role. Here we investigate feasibility efficacy prolonged blockade activity through adenovirus-mediated gene delivery a dimeric chimeric p55 TNFR-IgG fusion protein compare it therapy in established CIA. A single i.v. administration replication-deficient adenovirus yielded microgram serum levels ameliorated CIA for 10 days. Subsequently, benefit was lost rebound greater inflammatory observed despite continual presence bioactive TNFR protein. similar trend also mice injected directly with comparable amounts protein, whereas control adenovirus-encoding β-galactosidase or IgG1 did not significantly affect disease course. The mechanisms were investigated, augmented Ab response collagen type II identified as causes. Our results confirm cytokine inhibitors animal models autoimmune diseases investigational purposes highlight importance studies. Further investigations are needed optimize ways exploiting adenoviral RA.