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S. M. Whitcup, J. Gao, L. A. Wheeler, M. Calonge, M. E. Stern; Cytokine and Chemokine Profile in Experimental Autoimmune Uveitis. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2866.
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Uveitis is characterized by intraocular inflammation and can be caused by both infectious and non-infectious conditions. Pro-inflammatory cytokines and chemokines in both the aqueous humor and vitreous have been demonstrated to play important roles in the pathogenesis of uveitis. However, the expression of cytokine and chemokine levels in the eye with uveitis has not been fully elucidated. The aim of the current study was to define the profile of cytokines and chemokines in the vitreous and aqueous humor in an animal model of uveitis.
Experimental autoimmune uveitis (EAU) was induced by immunizing Lewis rats with uveitogenic peptide R16 generated from interphotoreceptor retinoid-binding protein (IRBP) (50 µg/rat) in CFA (Complete Freund’s Adjuvant). Fifteen days after immunization, aqueous humor and vitreous were collected to determine levels of a panel of cytokines and chemokines by multiplex Luminex assay (Millipore). For control purposes, samples were also collected from naïve rats and rats that received CFA alone.
When compared with normal controls, significant increases (ANOVA, p<0.05) in cytokine/chemokine concentrations were detected for IL-1α, IL-1β, IL-2, IL-6, IL-17, IFN-γ, RANTES, MCP-1, MIP-1α and VEGF in the vitreous; and IL-1, IL-2, IL-17, IFN-γ, RANTES, MCP-1 and MIP-1α levels in the aqueous humor of EAU rats. Greater than 3-fold increases were found for cytokines IL-1α, IL-6 and IL-17, and chemokines MCP-1, MIP-1α and RANTES in the vitreous of EAU rats as compared with CFA controls. The concentrations of IL-1β, IL-17, MCP-1, MIP-1α and RANTES were increased >3 fold in the aqueous humor. IL-6 and IL-17 (vitreous) and IL-1β and IL-17 (aqueous humor) were the most elevated cytokines. In contrast, IL-10 concentrations were significantly decreased (p<0.05) in both the aqueous humor and vitreous as compared with naïve control. TH2 cytokine levels, IL-4 and IL-5, were low and unchanged in the samples between control and diseased animals.
A panel of pro-inflammatory cytokines and chemokines were up-regulated in intraocular fluids of EAU rats. Intraocular levels of IL-6, IL-17, and IL-1β demonstrated the greatest increase while IL-10 was significantly decreased in eyes with inflammation. A number of inflammatory cytokines and chemokines are elevated in eyes with inflammation and may provide new targets for uveitis therapy.
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