Oligodeoxynucleotides containing CpG motifs (CpG-ODNs), administered systemically or into the airway, protect against eosinophilic airway inflammation in murine models of asthma; in this study, we evaluated the effects of oral administration of CpG-ODNs on atopic responses.

CpG-ODNs (10–1,000 μg) were administered by gastric gavage to mice at various time-points relative to sensitization to and challenge with the experimental allergen, ovalbumin (OVA); to evaluate the effect of CpG-ODNs on oral tolerance, OVA was coadministered with CpG-ODNs for some studies. Outcomes assessed included cellular airway inflammation, and OVA-specific immunoglobulin levels.

Oral administration of CpG-ODNs around the time of OVA-sensitization prevented the induction of eosinophilic airway inflammation in a dose-dependent manner. Induction of oral tolerance by the daily administration of high doses (20 mg) of OVA successfully prevented airway inflammation; this was not significantly affected by coadministration of CpG-ODNs. In this model, however, while both conditions suppressed OVA-specific IgG1, only mice that received both CpG-ODNs and OVA demonstrated enhanced IgG2a. In mice with previously-established OVA-induced airway inflammation, only those treated with both OVA and CpG-ODNs (but not treated with either agent alone) demonstrated tolerance to inhaled OVA, manifested by reduced airway. This desensitization also paralleled enhanced IgG2a production

These findings provide the first indication that oral administration of CpG-ODNs is effective in preventing onset of antigen-induced eosinophilic airway inflammation in murine model of asthma. More importantly, when CpG-ODNs was administered orally with antigen, successive oral tolerance was induced in established eosinophilic airway inflammation.