World Allergy Forum: Immune Intervention
Immunostimulatory DNA (ISS) Challenging Traditional Allergen Immunotherapy
Immunostimulatory DNA sequence (ISS or a CpG motif) can inhibit an ongoing Th2 response and induce de novo a Th1 response. Their ability to modulate the immediate and late phases of the allergic inflammation was evaluated in two related animal models. In a mouse model of ragweed (RW)-induced allergic conjunctivitis, systemic or mucosal (eye drops) administration of ISS oligonucleotide (ODN) after RW/alum sensitization and before (pre-priming) or with RW challenge inhibited both the immediate hypersensitivity response and the late phase cellular infiltration. ISS-ODN administration suppressed the subsequent RW specific Th1 response. Mechanistically, the ISS-induced anti-inflammatory and 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 response and the late phase cellular infiltration. In a mouse model of ovalbumin induced airway hyper-responsiveness ISS delivered prior (pre-priming) or with ovalbumin challenge significantly inhibits airway eosinophilia and reduces responsiveness to inhaled methacholine. The onset of the ISS effect on reducing the number of tissue eosinophils was for at least lasted 6 days. ISS was effective in inhibiting eosinophilic airway inflammation when administered either systemically (intraperitoneally), or mucosally (i.e. intranasally or intratracheally), to induce allergen specific IFN-g and to inhibit allergen specific IL-5 production. In both models ISS administration was more effective that dexamethasone in inhibiting the allergic responses. Thus, ISS-ODN is a novel anti-inflammatory and immunomodulatory agent that may provide an alternative to the current standard care of allergy.
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