Induction of oral tolerance by CpG-ODNs in a murine model of asthma - 25/08/11
Abstract |
Rationale |
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.
Methods |
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.
Results |
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
Conclusions |
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.
Le texte complet de cet article est disponible en PDF. Funding: NHLBI |
Vol 113 - N° 2S
P. S254 - février 2004 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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