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K Koizumi, S Doehmen, G Welsandt, B Kirchhof, V Poulaki, AM Joussen; The TNF-alpha Inhibitor Enbrel Reduces Leukocyte Adhesion, Vascular Leakage and Apoptotic Cell Death in Endotoxin Induced Uveitis In Vivo . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1557.
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Purpose:To investigate the effect of systemic injections of the TNF-alpha inhibitor Enbrel on the development of endotoxin-induced uveitis (EIU) in the rat. Methods:EIU was induced in Long Evans rats by a single footpad injection of lipopolysaccharide (LPS; 350 microg/kg) from Salmonella typhimurium. Rats were treated with a subcutaneous injection in the back of recombinant TNF receptor P75 (Enbrel) 24h before LPS injection. At 24 hours after LPS injection, Leukocyte adhesion was evaluated with SLO-Acridine Orange Fluography in vivo, Concanavalin A lectin staining in the flat mounted retina and quantified by myeloperoxidase activity assay. Vascular leakage was assessed by Evans blue extravasation. Retinal cell death was assayed in quantifying DNA fragmentation in the retina. Results:At 24 hours after LPS injection, significant clinical inhibition of ocular inflammation and fibrin deposition in the eye was observed in Enbrel-treated rats. Quantitative analysis of vascular leakage revealed a significant decrease after treatment with Enbrel. Retinal cell death quantification showed a significant decrease after treatment with the TNF-alpha-inhibitor. Conclusion:Anti-TNF-alpha treatment inhibits LPS-induced ocular inflammation with inhibition of vascular leakage in the eye. Enbrel might be useful in the treatment of autoimmune-uveitis.
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