Oral tolerance inhibits pulmonary eosinophilia in a cockroach allergen induced model of asthma: a randomized laboratory studyReportar como inadecuado




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Respiratory Research

, 11:160

First Online: 23 November 2010Received: 26 May 2010Accepted: 23 November 2010

Abstract

BackgroundAntigen desensitization through oral tolerance is becoming an increasingly attractive treatment option for allergic diseases. However, the mechanisms 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.

MethodsWe 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.

ResultsCRA 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.

ConclusionOur 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.

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Autor: Louis J Vaickus - Jacqueline Bouchard - Jiyoun Kim - Sudha Natarajan - Daniel G Remick

Fuente: https://link.springer.com/







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