Journal article
Mucosal immunotherapy with CpG oligodeoxynucleotides reverses a murine model of chronic asthma induced by repeated antigen exposure
American journal of physiology. Lung cellular and molecular physiology, Vol.285(5), pp.L1137-1146
11/2003
DOI: 10.1152/ajplung.00073.2003
PMID: 12857672
Abstract
Murine models of acute atopic asthma may be inadequate to study the effects of recurrent exposure to inhaled allergens, such as the epithelial changes seen in asthmatic patients. We developed a murine model in which chronic airway inflammation is maintained by repeated allergen [ovalbumin (OVA)] inhalation; using this model, we examined the response to mucosal administration of CpG DNA (oligonucleotides) and specific antigen immunotherapy. Mice repeatedly exposed to OVA developed significantly greater airway hyperresponsiveness and goblet cell hyperplasia, but not airway eosinophilia, compared with those exposed only twice. CpG-based immunotherapy significantly reversed both acute and chronic markers of inflammation as well as airway hyperresponsiveness. We further examined the effect of mucosal immunotherapy on the response to a second, unrelated antigen. Mice sensitized to both OVA and schistosome eggs, challenged with inhaled OVA, and then treated with OVA-directed immunotherapy demonstrated significant reduction of airway hyperresponsiveness and a moderate reduction in eosinophilia, after inhalation challenge with schistosome egg antigens. In this model, immunotherapy treatment reduced bronchoalveolar lavage (BAL) levels of Th2 cytokines (IL-4, IL-5, IL-13, and IL-10) without changing BAL IFN-gamma. Antigen recall responses of splenocytes from these mice demonstrated an antigen-specific (OVA) enhanced release of IL-10 from splenocytes of treated mice. These results suggest that CpG DNA may provide the basis for a novel form of immunotherapy of allergic asthma. Both antigen-specific and, to a lesser extent, antigen-nonspecific responses to mucosal administration of CpG DNA are seen.
Details
- Title: Subtitle
- Mucosal immunotherapy with CpG oligodeoxynucleotides reverses a murine model of chronic asthma induced by repeated antigen exposure
- Creators
- Vipul V Jain - Department of Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USAThomas R BusingaKunihiko KitagakiCaroline L GeorgePatrick T O'ShaughnessyJoel N Kline
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Lung cellular and molecular physiology, Vol.285(5), pp.L1137-1146
- DOI
- 10.1152/ajplung.00073.2003
- PMID
- 12857672
- ISSN
- 1040-0605
- eISSN
- 1522-1504
- Grant note
- HL-59324 / NHLBI NIH HHS
- Language
- English
- Date published
- 11/2003
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Civil and Environmental Engineering; Occupational and Environmental Health; Pathology; Internal Medicine
- Record Identifier
- 9984094670502771
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