Inhibitory Effects of Cyclosporine A Eye Drops on Symptoms in Late Phase and Delayed-Type Reactions in Allergic Conjunctivitis Models

• Published in: Biological & Pharmaceutical Bulletin 2010/08/01, Vol.33(8), pp.1314-1318
• Main Authors: Shii, Daisuke, Nakagawa, Shizu, Yoshimi, Miwa, Katsuta, Osamu, Oda, Tomoko, Nakamura, Masatsugu
• Format: Article
• Language: English
• Subjects: allergic conjunctivitis; Animals; Conjunctiva - drug effects; Conjunctiva - immunology; Conjunctiva - pathology; Conjunctivitis, Allergic - drug therapy; Conjunctivitis, Allergic - immunology; Conjunctivitis, Allergic - pathology; Cyclosporine - administration & dosage; Cyclosporine - pharmacology; Cyclosporine - therapeutic use; cyclosporine A; delayed-type reaction; Disease Models, Animal; Eosinophils - pathology; Freund's Adjuvant - immunology; Guinea Pigs; Hypersensitivity, Delayed - drug therapy; Hypersensitivity, Delayed - immunology; Hypersensitivity, Delayed - pathology; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - pharmacokinetics; Immunosuppressive Agents - therapeutic use; inflammatory cell infiltration; Instillation, Drug; late phase reaction; Leukocyte Count; Leukocytes, Mononuclear - pathology; Male; ocular symptom; Ophthalmic Solutions; Ovalbumin - immunology; Time Factors
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.33.1314

We investigated the efficacy of cyclosporine A (CyA) eye drops on ocular symptoms in late phase and delayed-type reactions in guinea pig allergic conjunctivitis models. An emulsion of ovalbumin (OVA) and Freund's complete adjuvant (FCA) was intraperitoneally injected into guinea pigs, and 15% OVA solution was applied topically to the eyes to elicit late phase reactions. Following the early phase reaction, increased scores for hyperemia, swelling, edema, and discharge were detected 6 h after antigen challenge, and CyA eye drops significantly inhibited the increase in scores for edema and discharge, the increase in the number of infiltrating inflammatory cells, and the percentage of eosinophils among polymorphonuclear leukocytes in conjunctival tissue. To induce delayed-type reactions, guinea pigs were sensitized by injecting FCA into the footpad, followed by injections of purified protein derivative into palpebral conjunctivae 24 d later. Increased scores for hyperemia, swelling, and discharge were detected 6 h after the induction of delayed-type allergy, and CyA eye drops significantly inhibited the increase in scores for hyperemia and swelling. In contrast, betamethasone sodium phosphate eye drops showed a tendency to inhibit the symptoms in both late phase and delayed-type reactions, or inflammatory cell infiltration in the late phase reaction, but the inhibition was not significant. These results suggest that CyA eye drops are useful for suppressing ocular symptoms in both late phase and delayed-type reactions in allergic conjunctivitis models.