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-beta -D-galactopyranoside (X-Gal) staining on frozen sections of eps 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(129/CD1, DBA1, and Balb/c), either of normal phenotype (+/+) or of deficiency (+/-, -/-) in the IL-18 gene which had been replaced by introduced genes including LacZ under the control of an IL-18 promotor.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 (va) 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 language | English |
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Pages (from-to) | 177-182 |
Number of pages | 5 |
Journal | Investigative Ophthalmology & Visual Science |
Volume | 42 |
Issue number | 1 |
Publication status | Published - 2001 |
Keywords
- EXPERIMENTAL AUTOIMMUNE UVEORETINITIS
- INTERFERON-GAMMA PRODUCTION
- IL-18-DEFICIENT MICE
- COSTIMULATORY FACTOR
- CYTOKINE PRODUCTION
- DENDRITIC CELLS
- TH2 CELLS
- T-CELLS
- INDUCTION
- INTERLEUKIN-18