IL-18 not required for IRBP peptide-induced EAU: Studies in gene-deficientmice

PURPOSE. Interleukin (IL)-18 has been described as a proinflammatory cytoki ne in rheumatoid arthritis and bacterial infectious diseases. The present s tudy was designed to determine the role of IL-18 in a model of ocular exper imental autoimmune uveitis (EAU). The initial studies were conducted to det ect the expression of IL-18 in normal mouse eye tissue, and the later studi es 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-b eta -D-galactopyranoside (X-Gal) staining on frozen sections of eps from mi ce (129/CD1, DBA1, and Balb/c), either of normal phenotype (+/+) or of defi ciency (+/-, -/-) in the IL-18 gene which had been replaced by introduced g enes including LacZ under the control of an IL-18 promotor.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) mic e after immunization with the uveitogenic antigen: interphotoreceptor retin al binding protein (IRBP) peptide 161-180. Lymphocyte proliferation and cyt okine production were also measured in WT and IL-18 KO DBA1 mice 15 days af ter 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 hist ologic characteristics, despite a generalized reduction of interferon (IFN) -gamma and tumor necrosis factor (TNF)-alpha on an IL-18(-/-) phenotype. DB A1 IL-18(-/-) also demonstrated reduced IL-10 production. Conclusions. The IL-18 gene is not necessary for the initiation or pathogen esis of EAU induced by IRBP peptide 161-180. IL-18 is expressed in the epit helial cells in iris, ciliary body, and retina in the eyes, but its role in the eye remains undetermined.