Modulation of Murine Allergic Rhinosinusitis by CpG Oligodeoxynucleotides

BACKGROUND: Allergic rhinosinusitis is characterized by eosinophilic inflammation of the upper airway, which is induced by TH-2 cytokines. CpG oligodeoxynucleotides (ODN) are known to induce TH-1 and to suppress TH-2 cytokines in a variety of settings, including murine models of asthma. OBJECTIVE: To examine the effect of CpG ODN in a murine model of upper airway allergic inflammation and to correlate with reduction of its manifestations of sneezing and nasal scratching. METHODS: BALB/c mice were sensitized using Ovalbumin (Ova) intraperitoneally and challenged with aerosolized Ova. CpG ODN were administered at the time of Ova sensitization. Outcomes measured included nasal symptoms, submucosal eosinophilia in the areas lined by respiratory or olfactory epithelium, and bone marrow eosinophilia. To delineate the mechanism of CpG ODN-induced suppression of eosinophilic inflammation, in vitro experiments were carried out to examine the effect of stimulation with Ova on splenocytes obtained from mice that were treated with CpG or control ODN (or no ODN) in vivo. Supernatant was collected after 72 hours of incubation and cytokines were measured by enzyme linked immunosorbent assay. RESULTS: CpG ODN administered at the time of Ova sensitization effectively abrogated nasal symptoms and eosinophilic upper airway inflammation compared with mice treated with control ODN or with no ODN. Cytokine data revealed that Ova sensitization suppressed IFN-gamma and induced IL-4 and IL-5 compared with non-sensitized mice. CpG ODN treatment reversed these effects. CONCLUSION: CpG ODN prevents the development of TH-2-mediated eosinophilic inflammation and symptoms in a murine model of allergic rhinosinusitis.