Cellular basis for rheumatoid inflammation.

Rheumatoid arthritis (RA) is a chronic idiopathic disease characterized by persistent inflammation of the synovium, local destruction of bone and cartilage, and a variety of systemic manifestations. Although the etiologic stimulus has not been identified, rheumatoid synovitis is characterized by persistent immunologic activity, with CD4(+)/CD29(+) memory T cells prominently involved. Many of the local and systemic manifestations of RA appear to result from the production of a variety of cytokines within the inflamed synovium. A number of other inflammatory mediators produced in the rheumatoid synovium, including arachidonic acid metabolites, vasoactive amines, platelet-activating factor, and complement cleavage products contribute to the inflammatory process. In addition, the local production of immunoglobulin and the autoantibody, rheumatoid factor, along with the local production of immune complexes and complement activation, play a major role in the destructive potential of rheumatoid synovitis. The driving force behind rheumatoid inflammation, however, is likely to be CD4(+) T cells responding to an antigenic epitope in the synovium in an HLA-DR restricted manner. Understanding the immunopathogenic process underlying rheumatoid inflammation should provide insight into approaches to control the disease effectively and specifically.