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Oral administration of CpG-ODNs suppresses antigen-induced asthma in mice.

Kitagaki K, Businga TR, Kline JN

Division of Pulmonary, Critical Care and Occupational Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, USA.

Oligodeoxynucleotides containing CpG motifs (CpG-ODNs) can protect against eosinophilic airway inflammation in asthma. Previously we have found that parenteral or mucosal administration of CpG-ODNs is effective in preventing (as well as reversing established) disease. In this study, we examined the effect of oral CpG-ODNs on the development of immune tolerance. Using an ovalbumin (OVA)-induced murine model of asthma, we found that CpG-ODNs, administered orally around the time of sensitization, prevented eosinophilic airway inflammation in a dose-dependent manner. Although oral co-administration of CpG-ODNs with OVA (known to induce tolerance) did not significantly change the inhibition of OVA-induced airway eosinophilia, it did modulate OVA-specific immunoglobulin responses: oral administration of OVA alone suppressed OVA-specific IgG1 production, but only mice that received CpG-ODNs demonstrated enhanced levels of OVA-specific IgG2c. Finally, we examined whether oral administration of CpG-ODNs, alone or with OVA, could reverse established eosinophilic airway inflammation. Again, neither OVA nor CpG-ODNs alone modulated established eosinophilic airway inflammation, but a combination of the OVA and CpG-ODNs successfully desensitized the mice. This desensitization was associated with suppression of OVA-specific IgE and enhancement of OVA-specific IgG2c production. These findings provide the first indication that oral administration of CpG-ODNs is effective in preventing and reversing antigen-induced eosinophilic airway inflammation. CpG-ODNs may be useful as a component of oral immunotherapy to promote tolerance in established asthma.

Published 17 January 2006 in Clin Exp Immunol, 143(2): 249-59.
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