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1 From the Department of Ophthalmology, University of Aberdeen Medical School Foresterhill, Aberdeen, United Kingdom; and the 2 Department of Immunology, University of Glasgow, United Kingdom.
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(129/CD1, DBA1, and Balb/c), either of normal phenotype (+/+) or of deficiency (±, -/-) in the IL-18 gene which had been replaced by introduced genes including LacZ under the control of an IL-18 promotor.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)-
and tumor necrosis factor
(TNF)-
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.
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