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

Hui-Rong Jiang, Xiao-qing Wei, Wanda Niedbala, Lynne Lumsden, Foo Yew Liew, John V. Forrester

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(129/CD1, DBA1, and Balb/c), either of normal phenotype (+/+) or of deficiency (+/-, -/-) in the IL-18 gene which had been replaced by introduced genes including LacZ under the control of an IL-18 promotor.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

Original languageEnglish
Pages (from-to)177-182
Number of pages6
JournalInvestigative Ophthalmology and Visual Science
Volume42
Issue number1
Publication statusPublished - 31 Jan 2001

Keywords

  • animals
  • autoimmune diseases
  • ciliary body
  • DNA primers
  • eye proteins
  • immunoenzyme techniques
  • interleukin-18
  • iris
  • lymphocyte activation
  • mice
  • mice, inbred BALB C
  • mice, inbred DBA
  • mice, knockout
  • peptide fragments
  • pigment epithelium of eye
  • retina
  • retinitis
  • retinol-binding proteins
  • T-Lymphocytes
  • Th1 Cells
  • uveitis

Cite this

Jiang, H-R., Wei, X., Niedbala, W., Lumsden, L., Liew, F. Y., & Forrester, J. V. (2001). IL-18 not required for IRBP peptide-induced EAU: studies in gene-deficient mice. Investigative Ophthalmology and Visual Science, 42(1), 177-182.