Enter your JBJS login information below. Please note that your username is the email address you provided when you registered. Activate your online account — Have a subscription? Click here to activate your account to receive online access to JBJS. NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. ‡Department of Orthopaedics, Massachusetts General Hospital, 55 Fruit Street, Gray 624, Boston, Massachusetts 02114-2617. E-mail address: firstname.lastname@example.org. Rheumatoid arthritis is incurable and difficult to treat with traditional pharmacological approaches. Because conventional drug therapy has clearly failed to conquer this distressing condition, novel therapeutic strategies are required. We are not referring to the numerous dubious alternative methods touted by the tabloid press but to new possibilities arising from the results of serious laboratory investigation. Recent research into the biology of rheumatoid arthritis has identified a number of proteins with promising antiarthritic properties , but their application to human disease is limited by difficulties in delivering them in a targeted, sustained fashion for extended periods of time. Most investigators would agree, in general terms, that the natural history of rheumatoid arthritis is as follows. In genetically susceptible individuals, an unknown environmental agent triggers an autoimmune response, which leads to the production of mediators, particularly cytokines, that drive the pathophysiological processes leading to the clinical manifestations of rheumatoid arthritis. Therapeutic intervention in this chain of events is possible at a number of sites. However, most efforts have been concentrated on modulating either T-lymphocyte responses or the activities of various arthritogenic cytokines Preclinical studies have confirmed that both of these approaches have merit. Agents that suppress the activities of lymphocyte costimulatory molecules have shown efficacy in animal models . Antibodies directed against lymphocyte antigens, such as CD4, have also shown antiarthritic effects, and several are currently being used in clinical trials . Most anticytokine strategies have centered on the suppression of interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) . Promising agents that do this include neutralizing antibodies, soluble receptors, and the interleukin-1 receptor antagonist protein (IL-1Ra). All have shown encouraging activity in animal models, and several are currently being evaluated in clinical trials in humans. The short-term effects of administration of antibodies directed … You may be able to gain access using your login credentials for your institution. Contact your library if you do not have a username and password. You may be able to gain access using your login credentials for your institution. Contact your library if you do not have a username and password. NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Source.