IL-18 not required for IRBP peptide-induced EAU: studies in gene-deficient mice

Invest Ophthalmol Vis Sci. 2001 Jan;42(1):177-82.

Abstract

Purpose: 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(129/CD1, DBA1, and Balb/c), either of normal phenotype (+/+) or of deficiency (+/-, -/-) in the IL-18 gene which had been replaced by introduced genes including LacZ under the control of an IL-18 promotor.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.

MeSH terms

  • Animals
  • Autoimmune Diseases / chemically induced
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / metabolism*
  • Autoimmune Diseases / pathology
  • Ciliary Body / metabolism
  • DNA Primers / chemistry
  • Eye Proteins
  • Immunoenzyme Techniques
  • Interleukin-18 / genetics
  • Interleukin-18 / physiology*
  • Iris / metabolism
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred DBA
  • Mice, Knockout
  • Peptide Fragments
  • Pigment Epithelium of Eye / metabolism
  • Retina / metabolism
  • Retinitis / chemically induced
  • Retinitis / immunology
  • Retinitis / metabolism*
  • Retinitis / pathology
  • Retinol-Binding Proteins
  • T-Lymphocytes / immunology
  • Th1 Cells / immunology
  • Uveitis / chemically induced
  • Uveitis / immunology
  • Uveitis / metabolism*
  • Uveitis / pathology

Substances

  • DNA Primers
  • Eye Proteins
  • Interleukin-18
  • Peptide Fragments
  • Retinol-Binding Proteins
  • interstitial retinol-binding protein