Impact of TNF inhibitors on rheumatoid arthritis

Abstract

Tumor Necrosis Factors (TNFs) have an important role in host defense against infections, while accumulating evidence suggest that overproduction of TNFs is involved in the pathogenesis of inflammatory disorders such as Rheumatoid Arthritis (RA). Early experiments have demonstrated that RA synovial cells produced an excess amount of TNF-α in vitro, and an anti-TNF-α monoclonal antibody inhibited not only TNF-α, but also subsequent production of IL-1, IL-6, and IL-8, suggesting that TNF-α is located upstream of the cytokine cascade. In addition, TNF-α transgenic (tg) mice developed erosive polyarticular arthritis, and the blockade of TNF-α significantly reduced the severity and the development of arthritis, and joint destruction. These results raise a possibility that the TNF inhibition is useful to manage inflammatory arthritis and has facilitated the clinical development of this approach. In this review, we introduce the physiological and pathological roles of TNFs, and summarize the efficacy and safety of the biological agents targeting on the tumor necrosis factor. The biological TNF inhibitors provide a great impact on our understanding of the pathogenesis, and have revolutionized our strategy in the management of inflammatory disorders with unknown etiology.