Are we seeking the correct targets for therapeutic intervention?

In this plenary symposium paper, the authors review the physiological development of rheumatoid arthritis, the rationale for the manipulation of the eicosanoid pathway, the inhibition of tissue destruction, and angiogenesis. They proceed to discuss immunotherapy under the headings of intercellular adhesion, the induction of tolerance, and novel immunomodulatory agents. They conclude that the palliative treatment of the acute aspect of inflammation will continue by necessity into the foreseeable future. Whilst the selectivity and tolerability of existing and novel modulators of the acute inflammatory response are being improved, the alleviation of joint destruction in the long-term rheumatoid patient will depend on the manipulation of those mechanisms involved in the maintenance of the chronic inflammatory process. The ultimate goal for the therapy of the future, namely remission, can now be pursued with good reason for success, with the application of modern molecular biological techniques which will increase not only our understanding of autoimmunity, but also our ability to manipulate the immune system with profound selectivity. Central to the realization of these goals are the long-term chronic models of inflammatory joint disease, such as granuloma-cartilage implants and polyarticular and monoarticular arthritides, which will be essential for the assessment of the therapeutic promise of these exciting new developments.