title: Effects of systemic and intravitreal TNF-α inhibition in experimental autoimmune uveoretinitis.
abstract: OBJECTIVE
  To investigate the effect of systemic or local TNF-α inhibition with etanercept on experimental autoimmune uveoretinitis (EAU).
  
  
  METHODS
  EAU was induced by immunizing B10.RIII mice with IRBPp161-180 or by adoptively transferring uveitogenic splenocytes. Mice received systemic or local treatment with etanercept in the afferent or efferent phase. For systemic treatment, mice were injected intraperitoneally. For local treatment, etanercept was injected intravitreally or subconjunctivally. Control mice received PBS. EAU scores were determined histologically. Splenic cells were assessed for [(3)H]thymidine incorporation. ELISA was performed to measure levels of cytokines produced by splenocytes. Vitreous cavity-associated immune deviation (VCAID) was induced by intravitreally injecting ovalbumin and evaluated by measuring DTH reaction.
  
  
  RESULTS
  After systemic treatment with etanercept in the afferent phase, EAU disease scores, IRBP-specific cell proliferation, and production of Th1, Th2, and Th17 cytokines were reduced. EAU also improved after intravitreal etanercept treatment in the afferent phase, with unaltered IRBP-specific proliferation, reduced IFN-γ, but increased IL-6 and IL-10 secretion. VCAID induction was impaired after intravitreal etanercept treatment. No amelioration of EAU or reduction in IRBP-specific cell response was found after systemic or intravitreal treatment in the efferent phase or after subconjunctival treatment. After adoptive transfer, etanercept- and PBS-treated recipients showed similar disease severity and antigen-specific proliferation of splenocytes.
  
  
  CONCLUSIONS
  It can be concluded that TNF-α participates mainly in the immunopathology in the induction phase of EAU. The mechanism of action underlying EAU improvement may be different for local and systemic etanercept treatment.
authors.affiliation: Ophtha-Lab, Department of Ophthalmology at St. Franziskus Hospital, Muenster, Germany. martin.busch@uveitis-zentrum.de
authors.forename: Martin
authors.initials: M
authors.lastname: Busch
authors.forename: Dirk
authors.initials: D
authors.lastname: Bauer
authors.forename: Maren
authors.initials: M
authors.lastname: Hennig
authors.forename: Susanne
authors.initials: S
authors.lastname: Wasmuth
authors.forename: Solon
authors.initials: S
authors.lastname: Thanos
authors.forename: Arnd
authors.initials: A
authors.lastname: Heiligenhaus
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D000068800:Etanercept; D005136:Eye Proteins; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D058449:Intravitreal Injections; D051379:Mice; D010047:Ovalbumin; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage; D012173:Retinitis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D012177:Retinol-Binding Proteins; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D015866:Uveitis, Posterior / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D014822:Vitreous Body / Q000378:metabolism; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D016207:Cytokines; D000068800:Etanercept; D005136:Eye Proteins; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D010047:Ovalbumin; D018124:Receptors, Tumor Necrosis Factor; D012177:Retinol-Binding Proteins; D014409:Tumor Necrosis Factor-alpha; D000099214:Retinol-Binding Proteins, Interstitial