This proposal is based on the hypothesis that cytokines have a role in differentiating between the various clinical phenotypes that comprise juvenile rheumatoid arthritis (JRA), the commonest autoimmune rheumatic disease of childhood. Differences in synovial cytokine expression in JRA are likely to complement those already documented with respect to HLA and T cell receptor genes and will also distinguish some types of JRA from rheumatoid arthritis (RA) in adults. It is hypothesized that, based on preliminary data, IL-4 and IL-10 will protect against the more erosive destructive forms of joint disease in JRA and that this effect will be much more clearly demonstrated by the introduction of quantitative methodology. The proposal is based on three specific aims summarized as follows: 1.1 To determine cytokine profiles in joint tissues and fluids of patients with pauci juvenile rheumatoid arthritis and to make comparison with other arthropathies as follows: 1.2. To study the cytokine profile in the clinical evolution of pauci JRA. 1.3. To determine the cellular sources of cytokines which contribute to the pathogenesis of pauci JRA.
These aims will be achieved through the use of quantitative methods RNase protection assays, ELISA and, for cellular sources, immunohistochemistry and FACS analysis. Very central to such studies is the availability of a very comprehensive synovial tissue bank now incorporated into the Cincinnati MAMDC. The tissue is added to on an ongoing basis. In the long term, these studies can lead to experimental protocols to explore the cellular mechanisms involved and help in the selection of therapeutic interventions with immune response modifiers in JRA. These interventions are likely to be different, in part, from those used in RA.
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