Open AccessBeneficial effects of tumour necrosis factor‐alpha (TNF‐α) blockade in rheumatoid arthritis (RA)
Author(s) -
MAINI R. N.,
ELLIOTT M. J.,
BRENNAN F. M.,
FELDMANN M.
Publication year - 1995
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1111/j.1365-2249.1995.tb08340.x
Subject(s) - rheumatoid arthritis , tumor necrosis factor alpha , immunology , blockade , medicine , necrosis , etanercept , receptor
SUMMARY 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.