Oral administration of CpG-ODNs suppresses antigen-induced asthma in mice.
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.
Kitagaki
K
K
Division of Pulmonary, Critical Care and Occupational Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, USA.
Businga
T R
TR
Kline
J N
JN
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000284:Administration, Oral; D000818:Animals; D000941:Antigens / Q000276:immunology; D001249:Asthma / Q000276:immunology*; D003888:Desensitization, Immunologic / Q000379:methods; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000276:immunology; D005260:Female; D007108:Immune Tolerance / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D012137:Respiratory System / Q000276:immunology
D000276:Adjuvants, Immunologic; D000941:Antigens; C408982:CPG-oligonucleotide; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D010047:Ovalbumin