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  • Title: Systemic or mucosal administration of immunostimulatory DNA inhibits early and late phases of murine allergic conjunctivitis.
    Author: Magone MT, Chan CC, Beck L, Whitcup SM, Raz E.
    Journal: Eur J Immunol; 2000 Jul; 30(7):1841-50. PubMed ID: 10940873.
    Abstract:
    Seasonal allergic conjunctivitis is one of the most common manifestations of allergic disease, affecting 15 % population in the United States annually. Short ragweed (RW) is a major cause of seasonal allergies. Immunostimulatory DNA sequences (ISS or CpG motifs) can inhibit an on-going Th2/allergic response and induce a de novo Th1 response. In this study, we investigated the ability of these ISS to modulate allergic responses in a RW-induced mouse model of seasonal allergic conjunctivitis. Systemic or mucosal administration of ISS oligonucleotide (ISS-ODN) after RW sensitization inhibited both the immediate hypersensitivity response and the late-phase cellular infiltration and induced a RW-specific Th1 response. ISS-ODN administration suppressed the rise of RW-specific IgE titers after repeated allergen challenge. Furthermore, ISS administration was more effective than dexamethasone in inhibiting the allergic response. Mechanistically, the ISS-induced immunomodulatory effects were abolished when mice were treated with anti-IL-12 neutralizing antibodies, suggesting a pivotal role for type 1 cytokines in the inhibition of both the immediate hypersensitivity and the late-phase cellular infiltration. Thus, ISS-ODN is a novel anti-inflammatory and immunomodulatory agent that significantly inhibits the allergic response and may provide an alternative to the current standard care of ocular allergy.
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