This project is designed to assess the mechanism by which endotoxin (bacterial lipopolysaccharide or LPS) induces uveitis in experimental animals and the relevance of this model to human disease. A non-invasive method to quantitate endotoxin induced ocular vascular permeability has been developed. This technique, ocular albumin fluorophotometry, is quite sensitive. The pharmacology of the disease has been studied in rats. Although indomethacin and/or cypropheptadine are effective in reducing the ocular vascular permeability that begins 3 hours after LPs, they are only modestly effective in reducing the cellular infiltrate that occurs 24 hours after LPS. Some of the anti-inflammatory effects of LPS have recently been reported including its ability to suppress immune complex induced-inflammation and the ability of endotoxin tolerance to inhibit endotoxin-induced increases in arachidonic acid metabolites and complement-derived chemotactic activity.
