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BACKGROUND: Eosinophils are important effector cells in severe allergic conjunctivitis such as vernal keratoconjunctivitis. Infiltration of eosinophils into the conjunctiva is mediated by type I and type IV allergic reactions. Cyclosporin A (CsA) eye drops are administered therapeutically for severe allergic conjunctivitis, but the mechanism by which CsA acts, that is, by inhibiting type I, type IV or both types of allergic reactions, is not known. We investigated whether CsA eye drops inhibit type I, type IV or both types of allergic reactions in the conjunctiva. METHODS: Experimental immune-mediated blepharoconjunctivitis (EC) was induced in BALB/c mice by either active immunization or passive immunization by transfer of ragweed (RW)-primed splenocytes and RW-specific IgE, followed by RW challenge to the conjunctiva. These mice were treated in eye drops with vehicle, 0.1% CsA, 0.5% CsA or 0.1% betamethasone five times (1 and 2 h before RW challenge and 1, 2 and 3 h after RW challenge). Twenty-four hours after the challenge, the conjunctivas were harvested for histological analysis to evaluate eosinophilic infiltration. To evaluate effects of CsA eye drops on systemic immune responses, sera and spleens were collected from actively immunized mice at the time of sacrifice to examine serum IgE levels and cellular immune responses, respectively. RESULTS: CsA eye drops significantly inhibited eosinophilic infiltration into the conjunctiva in actively immunized EC-developing mice compared with vehicle-treated mice. The CsA-induced inhibition was similar to inhibition induced by 0.1% betamethasone. Serum IgE levels and splenocyte responses in CsA-treated mice were equivalent to those in vehicle-treated mice. Betamethasone treatment inhibited eosinophilic infiltration into the conjunctiva induced by both splenocyte transfer and IgE transfer, while CsA treatment inhibited infiltration induced by splenocyte transfer. CONCLUSIONS: CsA eye drops inhibited eosinophilic infiltration into the conjunctiva without affecting systemic immune responses. CsA predominantly inhibits eosinophilic infiltration by interfering with the type IV allergic reaction in the conjunctiva.