Role of Interferon-γ in a Mouse Model of Allergic Conjunctivitis

Abstract

To characterize the effect of repeated topical exposure to allergen in a mouse model of allergic conjunctivitis and to determine the role of interferon-gamma (IFN-gamma) in the pathogenesis of allergic conjunctivitis. Wild-type BALB/c mice and IFN-gamma knockout (KO) BALB/c mice were sensitized in the footpad with short ragweed (SRW) allergen and challenged topically for seven consecutive days with SRW allergen. The number of splenic CD4(+) Th2 cells was determined by flow cytometry, and the cytokine profile of CD4(+) T cells from SRW-sensitized mice was evaluated by ELISA. The role of IFN-gamma in allergic conjunctivitis was also examined by timed in vivo neutralization with anti-IFN-gamma antibody. Allergic conjunctivitis was evaluated clinically and histopathologically. Repeated topical challenge with SRW allergen induced allergic conjunctivitis that was characterized by lid edema, chemosis, redness, and tearing. Histopathological analysis revealed a marked conjunctival infiltrate that was predominantly neutrophils and eosinophils. IFN-gamma KO mice and normal mice treated with anti-IFN-gamma antibody displayed milder clinical symptoms of allergic conjunctivitis and a 70% reduction in the number of eosinophils that infiltrated the conjunctiva. Spleen cells from SRW-sensitized mice contained a large population of cells that expressed the Th2 surface marker T1/ST2 and produced IL-4, -5, and -10 and IFN-gamma after stimulation with SRW allergen. Repeated topical application of SRW allergen induces a form of murine allergic conjunctivitis that mimics the human counterpart. IFN-gamma appears to contribute to the pathogenesis of murine allergic conjunctivitis at the effector phase, but not during the initial sensitization stage.