D Miyazaki1, G Liu, L Clark, S J Ono. 1. Schepens Eye Research Institute, Brigham and Women's Hospital and. Committee on Immunology, Harvard Medical School, Boston, Massachusetts, USA.
Abstract
PURPOSE: To evaluate the therapeutic potential of immunostimulatory sequence oligodeoxynucleotides (ISS-ODN) administration in ocular allergy, using a mouse model of ragweed-specific conjunctivitis. METHODS: A murine model of allergic conjunctivitis involving SWR/J mice sensitized and challenged with short ragweed was used to test immunostimulatory DNA sequences for therapeutic potential. ISS-ODN or control ODN (0.1 mg/mouse) was administered intraperitoneally or topically to the conjunctiva 3 days before final allergen challenge. Multiple parameters of clinical symptoms evident during the acute-phase reaction and the cellular components of the late-phase reaction were evaluated in both groups of mice. RESULTS: All parameters of clinical symptoms were markedly inhibited after intraperitoneal injection of ISS-ODN, whereas topical application to the conjunctiva did not inhibit clinical symptoms significantly. Remarkably, a single topical treatment with ISS-ODN (as well as by intraperitoneal injection) completely inhibited both eosinophilia and neutrophilia in the late-phase reaction. CONCLUSIONS: Systemic or conjunctival administration of ISS-ODN was shown to significantly inhibit allergic responses in this mouse model. This indicates that ISS-ODN may be an effective form of immunotherapy for this class of allergic disease.
PURPOSE: To evaluate the therapeutic potential of immunostimulatory sequence oligodeoxynucleotides (ISS-ODN) administration in ocular allergy, using a mouse model of ragweed-specific conjunctivitis. METHODS: A murine model of allergic conjunctivitis involving SWR/J mice sensitized and challenged with short ragweed was used to test immunostimulatory DNA sequences for therapeutic potential. ISS-ODN or control ODN (0.1 mg/mouse) was administered intraperitoneally or topically to the conjunctiva 3 days before final allergen challenge. Multiple parameters of clinical symptoms evident during the acute-phase reaction and the cellular components of the late-phase reaction were evaluated in both groups of mice. RESULTS: All parameters of clinical symptoms were markedly inhibited after intraperitoneal injection of ISS-ODN, whereas topical application to the conjunctiva did not inhibit clinical symptoms significantly. Remarkably, a single topical treatment with ISS-ODN (as well as by intraperitoneal injection) completely inhibited both eosinophilia and neutrophilia in the late-phase reaction. CONCLUSIONS: Systemic or conjunctival administration of ISS-ODN was shown to significantly inhibit allergic responses in this mouse model. This indicates that ISS-ODN may be an effective form of immunotherapy for this class of allergic disease.
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