Beneficial effects of tumour necrosis factor-alpha (TNF-α) blockade in rheumatoid arthritis (RA)

Abstract

The biological properties of TNF-α make it a candidate therapeutic target in RA. Our studies have demonstrated that TNF-α and its receptors are up-regulated and co-expressed in the synovium and cartilage-pannus junction of RA joints. Neutralizing TNF-α antibodies reduce the production of the many pro-inflammatory cytokines, including IL-1 and granulocyte-macrophage colony-stimulating factor (GM-CSF), produced by mononuclear cells from RA in culture. When injected into DBA/1 mice with collagen-induced arthritis and TNF-α transgenic mice with arthritis, anti-TNF MoAbs decrease inflammatory damage of joints. Clinical trials employing cA2, a chimaeric anti-TNF-α MoAb, in open-label and randomized placebo-controlled studies have demonstrated a dose-dependent efficacy with impressive improvement in disease activity and acute-phase responses lasting several weeks. We conclude that TNF-α is a critical mediator of inflammation in RA, and is an important therapeutic target in this disease.