Systemic or mucosal administration of immunostimulatory DNA inhibits earlyand late phases of murine allergic conjunctivitis

Seasonal allergic conjunctivitis is one of the most common manifestations o f allergic disease, affecting 15 % population in the United States annually . Short ragweed (RW) is a major cause of seasonal allergies. Immunostimulat ory 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 mou se model of seasonal allergic conjunctivitis. Systemic or mucosal administr ation of ISS oligonucleotide (ISS-ODN) after RW sensitization inhibited bot h the immediate hypersensitivitiy response and the late-phase cellular infi ltration and induced a RW-specific Th1 response. ISS-ODN administration sup pressed the rise of RW-specific IgE titers after repeated allergen challeng e. Furthermore, ISS administration was more effective than dexamethasone in inhibiting the allergic response. Mechanistically, the ISS-induced immunom odulatory effects were abolished when mice were treated with anti-IL-12 neu tralizing antibodies, suggesting a pivotal role for type 1 cytokines in the inhibition of both the immediate hypersensitivity and the late-phase cellu lar infiltration. Thus, ISS-ODN is a novel antiinflammatory and immunomodul atory agent that significantly inhibits the allergic response and may provi de an alternative to the current standard care of ocular allergy.