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Induction of oral tolerance by CpG-ODNs in a murine model of asthma
S254 Abstracts
J ALLERGY CLIN IMMUNOL FEBRUARY 2004
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 OVAsensitization 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 OVAinduced 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 antigeninduced 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. Funding: NHLBI
MONDAY 915
Induction of Oral Tolerance by CpG-ODNs in a Murine Model of Asthma
J. N. Kline, K. Kitagaki, T. Businga; Pulmonary Medicine, University of Iowa, Iowa City, IA. RATIONALE: Oligodeoxynucleotides containing CpG motifs (CpGODNs), administered systemically or into the airway, protect against eosinophilic airway inflammation in murine models of asthma; in this
J ALLERGY CLIN IMMUNOL FEBRUARY 2004
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 OVAsensitization 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 OVAinduced 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 antigeninduced 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. Funding: NHLBI
MONDAY 915
Induction of Oral Tolerance by CpG-ODNs in a Murine Model of Asthma
J. N. Kline, K. Kitagaki, T. Businga; Pulmonary Medicine, University of Iowa, Iowa City, IA. RATIONALE: Oligodeoxynucleotides containing CpG motifs (CpGODNs), administered systemically or into the airway, protect against eosinophilic airway inflammation in murine models of asthma; in this