title: IL-18 not required for IRBP peptide-induced EAU: studies in gene-deficient mice.
abstract: OBJECTIVE
  Interleukin (IL)-18 has been described as a proinflammatory cytokine in rheumatoid arthritis and bacterial infectious diseases. The present study was designed to determine the role of IL-18 in a model of ocular experimental autoimmune uveitis (EAU). The initial studies were conducted to detect the expression of IL-18 in normal mouse eye tissue, and the later studies investigated induction of EAU in mice with an IL-18(-/-) phenotype.
  
  
  METHODS
  IL-18 detection was performed by using 5-bromo-4-chloro-3-indoyl-ss--D-galactopyranoside (X-Gal) staining on frozen sections of eyes from mice (129/CD1, DBA1, and Balb/c), either of normal phenotype (+/+) or of deficiency (+/-, -/-) in the IL-18 gene which had been replaced by introduced genes including LacZ under the control of an IL-18 promotor. Severity of EAU was assessed in DBA1 and 129/CD1 wild-type (WT) or IL-18 knockout (KO) mice after immunization with the uveitogenic antigen: interphotoreceptor retinal binding protein (IRBP) peptide 161-180. Lymphocyte proliferation and cytokine production were also measured in WT and IL-18 KO DBA1 mice 15 days after immunization.
  
  
  RESULTS
  IL-18 is constitutively expressed in the epithelial cells in iris, ciliary body, and retina. EAU-resistant mice (129/CD1) with an IL-18(-/-) phenotype remained resistant after immunization with IRBP peptide (P161-180). However, EAU-susceptible mice (DBA1) exhibited disease with similar histologic characteristics, despite a generalized reduction of interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha on an IL-18(-/-) phenotype. DBA1 IL-18(-/-) also demonstrated reduced IL-10 production.
  
  
  CONCLUSIONS
  The IL-18 gene is not necessary for the initiation or pathogenesis of EAU induced by IRBP peptide 161-180. IL-18 is expressed in the epithelial cells in iris, ciliary body, and retina in the eyes, but its role in the eye remains undetermined.
authors.affiliation: Department of Ophthalmology, University of Aberdeen Medical School Foresterhill, Aberdeen, United Kingdom.
authors.forename: H R
authors.initials: HR
authors.lastname: Jiang
authors.forename: X
authors.initials: X
authors.lastname: Wei
authors.forename: W
authors.initials: W
authors.lastname: Niedbala
authors.forename: L
authors.initials: L
authors.lastname: Lumsden
authors.forename: F Y
authors.initials: FY
authors.lastname: Liew
authors.forename: J V
authors.initials: JV
authors.lastname: Forrester
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002924:Ciliary Body / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D005136:Eye Proteins; D007124:Immunoenzyme Techniques; D020382:Interleukin-18 / Q000235:genetics / Q000502:physiology*; D007498:Iris / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D010446:Peptide Fragments; D010857:Pigment Epithelium of Eye / Q000378:metabolism; D012160:Retina / Q000378:metabolism; D012173:Retinitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D012177:Retinol-Binding Proteins; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014605:Uveitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D017931:DNA Primers; D005136:Eye Proteins; D020382:Interleukin-18; D010446:Peptide Fragments; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial