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Impressum
The TNF-alpha inhibitor Enbrel reduces inflammation, vascular leakage and apoptotic cell death in endotoxin induced uveitis in vivo
Koizumi K., Doehmen S., Welsandt G., Kirchhof B., Poulaki V., Joussen A. M.
Dept. of Vitreoretinal Surgery, University of Cologne, Germany and Massachusetts Eye and Ear Infirmary, Harvard Medical School; Boston MA, USA
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
TNFReceptor P75 (Enbrel) 24h before LPS injection. At 24 hours after LPS
injection, Leukocyte adhesion was evaluated with SLO-Acridine Orange Fluography.
Vascular leakage was assessed by Evans blue extravasation. The expression
of nitric oxide synthase (NOS)-II in ocular tissues was determined by
an ELISA Technique. 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. The expression
of nitric oxide synthase was reduced in the retinal tissue and the iris.
Retinal cell death quantification showed a significant decrease after
treatment with the TNF-alpha-inhibitor.
Conclusions: Anti-TNF-alpha treatment inhibits LPS-induced ocular
inflammation with inhibition of nitrite release and vascular leakage in
the eye. These results confirm the role of the NO pathway in the pathogenesis
of EIU and suggest the involvement of TNF in the regulation of ocular
inflammation. Enbrel might be useful in the treatment of autoimmune-uveitis.
JDFI Jo 3-2000-192 und Ernst-und-Berta-Grimmke Stiftung and Meyer-Schwarting
Stiftung