title: Intravitreal injection of anti-Interleukin (IL)-6 antibody attenuates experimental autoimmune uveitis in mice.
abstract: To evaluate the effect of an intravitreally applied anti-IL-6 antibody for the treatment of experimental autoimmune uveitis (EAU).
  
  
  
  EAU was induced in female B10.RIII mice by Inter-Photoreceptor-Binding-Protein (IRBP) in complete Freund's adjuvant, boosted by Pertussis toxin. Single blinded intravitreal injections of anti-IL-6 antibody were applied 5-7days as well as 8-10days (3day interval) after EAU induction into the randomized treatment eye and phosphate buffered saline (PBS) into the fellow control eye. Clinical and fluorescein angiography scoring (6 EAU grades) was done at each injection day and at enucleation day 14. Enucleated eyes were either scored histologically (6 EAU grades) or examined by ELISA for levels of IL-6, IL-17 and IL-6 soluble Receptor (sIL-6R).
  
  
  
  Uveitis developed in all 12 mice. Clinical uveitis score was significantly reduced (p=0.035) in treated eyes (median 2.0, range 0-4.0, n=12) compared to the fellow control eyes (median 3.0, range 1.0-4.0, n=12). Angiography scores were reduced in 9/12 treated eyes and histological scores in 3/4 treated eyes compared to the fellow control eyes. Cytokine levels were determined in 8 mice, of which 4 responded to anti-IL-6 treatment and 4 did not respond. All mice responding to treatment had a significant reduction of IL-6 (p<0.01) and IL-17 (p=0.01) levels in treated eyes compared to the fellow control eyes. This difference was not seen in non-responding mice.
  
  
  
  Intravitreal anti-IL-6 treatment significantly attenuates experimental autoimmune uveitis in mice. EAU activity correlates with ocular IL-6 and IL-17 levels.
authors.affiliation: Christian-Albrechts-University of Kiel, University Medical Center, Department of Ophthalmology, Kiel, Germany. Electronic address: jan.tode@uksh.de.
authors.forename: Jan
authors.initials: J
authors.lastname: Tode
authors.affiliation: Christian-Albrechts-University of Kiel, University Medical Center, Department of Ophthalmology, Kiel, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Richert
authors.affiliation: Christian-Albrechts-University of Kiel, University Medical Center, Department of Ophthalmology, Kiel, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Koinzer
authors.affiliation: Christian-Albrechts-University of Kiel, University Medical Center, Department of Ophthalmology, Kiel, Germany.
authors.forename: Alexa
authors.initials: A
authors.lastname: Klettner
authors.affiliation: Christian-Albrechts-University of Kiel, Institute of Biochemistry, Kiel, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Pickhinke
authors.affiliation: Christian-Albrechts-University of Kiel, Institute of Biochemistry, Kiel, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Garbers
authors.affiliation: Christian-Albrechts-University of Kiel, Institute of Biochemistry, Kiel, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Rose-John
authors.affiliation: Christian-Albrechts-University of Kiel, University Medical Center, Department of Ophthalmology, Kiel, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Nölle
authors.affiliation: Christian-Albrechts-University of Kiel, University Medical Center, Department of Ophthalmology, Kiel, Germany.
authors.forename: Johann
authors.initials: J
authors.lastname: Roider
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000628:therapy*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005136:Eye Proteins / Q000032:analysis / Q000276:immunology; D005260:Female; D005620:Freund's Adjuvant; D007167:Immunotherapy; D020381:Interleukin-17 / Q000032:analysis / Q000276:immunology; D015850:Interleukin-6 / Q000032:analysis / Q000276:immunology; D058449:Intravitreal Injections; D051379:Mice; D037342:Pertussis Toxin / Q000008:administration & dosage; D011897:Random Allocation; D014605:Uveitis / Q000139:chemically induced / Q000276:immunology / Q000628:therapy*; D000093242:Interleukin-6 Inhibitors
chemical_list: D000906:Antibodies; D005136:Eye Proteins; D005620:Freund's Adjuvant; D020381:Interleukin-17; D015850:Interleukin-6; D037342:Pertussis Toxin; D000093242:Interleukin-6 Inhibitors
keywords: Anti-IL-6; Experimental autoimmune uveitis, EAU; IL-6; Intraocular; Intravitreal