The mechanisms involved in the immunopathology of recurrent uveitis are not yet clearly understood. Our hypothesis is that a small number of resident immunocompetent cells is responsible for amplification of the chronic ocular inflammatory response which is mainly composed of non-antigen-specific inflammatory cells. In the proposed investigations we will be concerned with two aspects which underlie this hypothesis: 1) the role of immunologically committed memory cells; and 2) the effects of membrane antigens, lymphokines, and cytokines in amplification of the inflammatory response. In the rabbit model system, we have recently published data confirming the presence of Macrophage Ia Recruiting Factor (MIRF) in the aqueous from uveitic eyes. The experiments proposed herein will investigate the intraocular production of a variety of lymphokines including IL-1, IL-2, and interferon in both primary and recurrent uveitis. In other experiments we will passively immunize the eye using syngeneic donor immune lymphocytes or lymphoid tissue. Under those circumstances, intravenous challenge with specific antigen in these otherwise naive recipients should result in uveitis. The time sequence for these experiments will allow us to mimic the striking immunologic memory associated with human recurrent ocular inflammatory disease. We also intend to block both the induction and recall phase of antigen-induced uveitis. First, we will attempt to inhibit the ability of the sensitized lymphocyte to produce lymphokine mediators, using the local infusion of pharmacological agents including theophylline to effectively block the amplifying effects emanating from these cells. In the second phase of these experiments on inhibition of uveitis, we hope to demonstrate that lipocortin, a phospholipase inhibitory protein, will have a marked anti-inflammatory effect. We postulate that lipocortin will locally inhibit the release of free arachadonic acid from phospholipids through the action of phospholipases and thus prevent prostaglandin synthesis.
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