title: Cyclosporin A inhibits eosinophilic infiltration into the conjunctiva mediated by type IV allergic reactions.
abstract: 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.
authors.affiliation: Department of Ophthalmology, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku-city, Japan. fukusima@med.kochi-u.ac.jp
authors.forename: Atsuki
authors.initials: A
authors.lastname: Fukushima
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Waka
authors.initials: W
authors.lastname: Ishida
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Fukata
authors.forename: Fu-Tong
authors.initials: FT
authors.lastname: Liu
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Ueno
mesh_terms: D000818:Animals; D001623:Betamethasone / Q000008:administration & dosage; D001762:Blepharitis / Q000276:immunology / Q000517:prevention & control; D002465:Cell Movement / Q000187:drug effects*; D003233:Conjunctivitis, Allergic / Q000276:immunology / Q000517:prevention & control*; D016572:Cyclosporine / Q000008:administration & dosage*; D016207:Cytokines / Q000032:analysis; D004804:Eosinophils / Q000502:physiology*; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000517:prevention & control*; D007116:Immunization, Passive; D007124:Immunoenzyme Techniques; D007073:Immunoglobulin E / Q000097:blood; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009883:Ophthalmic Solutions / Q000008:administration & dosage; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D009883:Ophthalmic Solutions; D007073:Immunoglobulin E; D016572:Cyclosporine; D001623:Betamethasone