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

Abstract

The biological properties of TNF-alpha make it a candidate therapeutic target in RA. Our studies have demonstrated that TNF-alpha and its receptors are up-regulated and co-expressed in the synovium and cartilage-pannus junction of RA joints. Neutralizing TNF-alpha 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-alpha transgenic mice with arthritis, anti-TNF MoAbs decrease inflammatory damage of joints. Clinical trials employing cA2, a chimaeric anti-TNF-alpha 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-alpha is a critical mediator of inflammation in RA, and is an important therapeutic target in this disease.

• Authors: R N Maini, M J Elliott, F M Brennan, M Feldmann
• Journal: Clinical and experimental immunology (Clin Exp Immunol) Vol. 101 Issue 2 Pg. 207-12 (Aug 1995) ISSN: 0009-9104 [Print] England
• PMID: 7648705 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antibodies, Monoclonal
• Tumor Necrosis Factor-alpha

Topics

• Antibodies, Monoclonal (therapeutic use)
• Arthritis, Rheumatoid (therapy)
• Humans
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, immunology)