title: Targeting TNF alpha for the therapy of rheumatoid arthritis.
abstract: Our pre-clinical studies have demonstrated a pathogenic role for TNF alpha in RA. Firstly, TNF alpha and its receptors are upregulated and co-expressed in the synovium and cartilage-pannus junction of RA joints. Secondly, mononuclear cells from RA joints maintained in culture produce many cytokines with pro-inflammatory activity, including TNF alpha. Neutralizing TNF alpha antibodies in vitro reduces the production of these pro-inflammatory cytokines, including IL-1, IL-8, and GM-CSF. Thirdly, when injected into arthritic DBA/l mice with collagen-induced arthritis, monoclonal anti-TNF antibodies decrease inflammatory damage of joints. Clinical trials employing cA2, a monoclonal chimeric anti-TNF alpha antibody, 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.affiliation: Kennedy Institute of Rheumatology, London, U.K.
authors.forename: R N
authors.initials: RN
authors.lastname: Maini
authors.forename: M
authors.initials: M
authors.lastname: Elliott
authors.forename: F M
authors.initials: FM
authors.lastname: Brennan
authors.forename: R O
authors.initials: RO
authors.lastname: Williams
authors.forename: M
authors.initials: M
authors.lastname: Feldmann
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000628:therapy*; D002986:Clinical Trials as Topic; D006801:Humans; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha