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Oral Tolerance Inhibits Pulmonary Eosinophilia in a Cockroach Allergen Induced Model of Asthma: A Randomized Laboratory Study

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dc.contributor.author Vaickus, Louis J en_US
dc.contributor.author Bouchard, Jacqueline en_US
dc.contributor.author Kim, Jiyoun en_US
dc.contributor.author Natarajan, Sudha en_US
dc.contributor.author Remick, Daniel G en_US
dc.date.accessioned 2012-01-11T23:19:34Z
dc.date.available 2012-01-11T23:19:34Z
dc.date.copyright 2010 en_US
dc.date.issued 2010-11-23 en_US
dc.identifier.citation Vaickus, Louis J, Jacqueline Bouchard, Jiyoun Kim, Sudha Natarajan, Daniel G Remick. "Oral tolerance inhibits pulmonary eosinophilia in a cockroach allergen induced model of asthma: a randomized laboratory study" Respiratory Research 11(1):160. (2010) en_US
dc.identifier.issn 1465-993X en_US
dc.identifier.uri http://hdl.handle.net/2144/3340
dc.description.abstract BACKGROUND. Antigen desensitization through oral tolerance is becoming an increasingly attractive treatment option for allergic diseases. However, the mechanism(s) by which tolerization is achieved remain poorly defined. In this study we endeavored to induce oral tolerance to cockroach allergen (CRA: a complex mixture of insect components) in order to ameliorate asthma-like, allergic pulmonary inflammation. METHODS. We compared the pulmonary inflammation of mice which had received four CRA feedings prior to intratracheal allergen sensitization and challenge to mice fed PBS on the same time course. Respiratory parameters were assessed by whole body unrestrained plethysmography and mechanical ventilation with forced oscillation. Bronchoalveolar lavage fluid (BAL) and lung homogenate (LH) were assessed for cytokines and chemokines by ELISA. BAL inflammatory cells were also collected and examined by light microscopy. RESULTS. CRA feeding prior to allergen sensitization and challenge led to a significant improvement in respiratory health. Airways hyperreactivity measured indirectly via enhanced pause (Penh) was meaningfully reduced in the CRA-fed mice compared to the PBS fed mice (2.3 ± 0.4 vs 3.9 ± 0.6; p = 0.03). Directly measured airways resistance confirmed this trend when comparing the CRA-fed to the PBS-fed animals (2.97 ± 0.98 vs 4.95 ± 1.41). This effect was not due to reduced traditional inflammatory cell chemotactic factors, Th2 or other cytokines and chemokines. The mechanism of improved respiratory health in the tolerized mice was due to significantly reduced eosinophil numbers in the bronchoalveolar lavage fluid (43300 ± 11445 vs 158786 ± 38908; p = 0.007) and eosinophil specific peroxidase activity in the lung homogenate (0.59 ± 0.13 vs 1.19 ± 0.19; p = 0.017). The decreased eosinophilia was likely the result of increased IL-10 in the lung homogenate of the tolerized mice (6320 ± 354 ng/mL vs 5190 ± 404 ng/mL, p = 0.02). CONCLUSION. Our results show that oral tolerization to CRA can improve the respiratory health of experimental mice in a CRA-induced model of asthma-like pulmonary inflammation by reducing pulmonary eosinophilia. en_US
dc.description.sponsorship Boston University School of Medicine (Immunology Training Grant Program); National Institute of Environmental Health Sciences (5R01ES013538-04); National Institutes of Health (2T32AI007309-21A1) en_US
dc.language.iso en en_US
dc.publisher BioMed Central en_US
dc.rights Copyright 2010 Vaickus et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. en_US
dc.title Oral Tolerance Inhibits Pulmonary Eosinophilia in a Cockroach Allergen Induced Model of Asthma: A Randomized Laboratory Study en_US
dc.type article en_US
dc.identifier.doi 10.1186/1465-9921-11-160 en_US
dc.identifier.pubmedid 21092270 en_US
dc.identifier.pmcid 3016351 en_US


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