Collagen-induced arthritis in mice: a major role for tumor necrosis factor-alpha.
Collagen-induced arthritis is the most widely used animal model for the evaluation of novel therapeutic strategies for rheumatoid arthritis. The disease is induced by immunization of genetically susceptible strains of mice or rats with type II collagen in adjuvant. Susceptibility to collagen-induced arthritis is associated with major histocompatibility complex (MHC) class II genes, although non-MHC genes also play a role. Both B- and T-lymphocytes are important in the pathogenesis of collagen-induced arthritis, with the peak of the T-cell response occurring around the time of disease onset. Histopathological assessment of the joints of animals with collagen-induced arthritis reveal a proliferative synovitis with infiltration of polymorphonuclear and mononuclear cells, the formation of an erosive pannus, cartilage degradation, and fibrosis. As in human rheumatoid arthritis, a number of both pro- and anti-inflammatory cytokines are expressed in the joints of mice with collagen-induced arthritis, including tumor necrosis factor-alpha (TNFalpha) and interleukin (IL)-1beta, IL-6, IL-1Ra, IL-10, and transforming growth factor beta. The use transgenic and knockout strains of mice, as well as biological inhibitors, have revealed important pathological roles for multiple cytokines. Of these, TNFalpha emerged as a valid therapeutic target for rheumatoid arthritis and this led to the setting up of clinical trials of anti-TNFalpha antibody therapy. Three anti-TNFalpha biologics(infliximab, etanercept, and adalimumab) are now approved for use and TNFalpha blockade therefore represents an important advance in our ability to treat rheumatoid arthritis.
Williams
Richard O
RO
Kennedy Institute of Rheumatology Division, Imperial College London, London, UK.
D000276:Adjuvants, Immunologic / Q000633:toxicity; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002986:Clinical Trials as Topic; D024043:Collagen Type II / Q000633:toxicity; D016207:Cytokines / Q000276:immunology*; D005802:Genes, MHC Class II / Q000276:immunology; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D024043:Collagen Type II; D016207:Cytokines