Immunotherapy in collagen-induced arthritis: past, present, and future

Type II collagen-induced arthritis has played a critical role in the development of novel approaches to the treatment of rheumatoid arthritis. The model has provided insights into autoimmune mechanisms relevant to the pathogenesis of joint disease and permitted the identification of potential targets for arthritis therapy. Notably, the model excelled in the development of cytokine inhibition for rheumatoid arthritis, with investigations demonstrating that a complex network of cytokine interactions regulate the autoimmune response to collagen. Recent studies of collagen-induced arthritis provide indications of novel approaches to disease intervention. New directions include modulation of the recognition and presentation of autoantigens, inhibition of specific T cell subsets responding to autoantigens, blocking of stimulatory cosignals at the cell surface, decoys for cytoplasmic and nuclear activation signals, interference with lymphocyte migration to the synovial joint, and reduction of the mediators of joint destruction. These approaches can be implemented through gene therapy, biological response mediators, or classic pharmacological intervention.