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Martin Busch, Dirk Bauer, Maren Hennig, Susanne Wasmuth, Solon Thanos, Arnd Heiligenhaus; Effect of Systemic or Intravitreal Anti Tumor Necrosis Factor-alpha Treatment in Experimental Autoimmune Uveoretinitis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2277.
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To investigate the effect of systemic or local tumor necrosis factor-alpha (TNF-α) -inhibition with etanercept on experimental autoimmune uveoretinitis (EAU).
EAU was induced in B10.RIII mice by subcutaneous injection of IRBP peptide 161-180 together with CFA, and additional PTX intraperitoneally. For systemic treatment, mice were injected intraperitoneally with 200 µg of etanercept in the afferent phase on days -1, 1, 3, and 5 post immunization (p. i.), or in the efferent stage on days 6, 9, and 12 p. i. For intraocular treatment, 50 µg of etanercept were injected intravitreally in the afferent phase on days -1, 2, and 5 p.i., or in the efferent phase on days 6, 9, and 12 p.i. Control mice received PBS. At least 10 mice were used for each group. On day 21 p. i., eyes were examined histologically respective the EAU scores. Cells collected from spleens were assessed for antigen specific proliferative response (3[H] thymidin incorporation).
After systemic treatment with etanercept in the afferent phase, EAU disease scores and IRBP-antigen specific proliferation of splenocytes were significantly reduced. Improved EAU scores were also found after intravitreal treatment with etanercept in the afferent phase, but without reduced IRBP T cell proliferation. No amelioration of EAU was found after systemic or intravitreal treatment in the efferent phase.
Since systemic or local TNF-alpha inhibition in the afferent phase improves histological disease, but not in the efferent phase after immunization, we conclude that TNF-α participates mainly in the immunopathology in the induction phase of EAU.
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