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A novel therapeutic approach for systemic inflammatory diseases such as rheumatoid arthritis is directed towards adhesion receptors. Interactions mediated by adhesion receptors govern the recruitment of inflammatory cells into inflammatory sites, such as the rheumatoid synovium, and the activation of immunocompetent cells. Therefore, adhesion receptors may be valuable therapeutic targets for immunologically driven, systemic inflammatory diseases such as rheumatoid arthritis. For example, antiadhesion therapy might hinder the ability of arthritogenic T cells to access the synovium and perpetuate the inflammatory response. Alternatively, inhibition of adhesion receptors might modulate the function of immunocompetent cells already present in the inflamed synovium, thereby attenuating the progression of disease. The potential utility of antiadhesion therapy in inflammatory arthritis has been confirmed in various animal models. Moreover, an antibody directed against the adhesion receptor intercellular adhesion molecule-1 (ICAM-1) has been successfully utilised in several open trials in patients with rheumatoid arthritis. Recent progress in this exciting discipline is reviewed, and relevant future directions are considered.