PREVENTION OF LUNG EOSINOPHILIC INFLAMMATION BY ORAL TOLERANCE

Airway inflammation plays a major role in human asthma. Increasing evi dence points to a close correlation between eosinophil infiltration an d allergic lung disease. A new murine model of eosinophilic lung infla mmation has recently been developed; it consists of immunizing mice wi th small fragments of solidified hen egg white implanted (EWI) into th e subcutaneous tissue. In this model, which is further characterized h ere, mice challenged with ovalbumin (OVA) present an intense and persi stent lung eosinophilia, as well as histopathological findings that re semble human asthma. In the present work, the effect of oral tolerance on the development of allergic lung inflammation in B6 mice immunized with antigen plus adjuvant or with EWI is investigated. It was found that in mice rendered orally tolerant by previous exposure to antigen in the drinking water, the T-helper type 2 cell (Th2)-associated aller gic responses in both protocols of immunization were almost completely abolished. The allergic responses were assessed by pulmonary and bone marrow eosinophilia, lung histopathology and antigen-specific IgE and IgG1 production, These findings provide the first indication that Th2 -associated lung pathology can be prevented by oral tolerance. (C) 199 8 Elsevier Science B.V. All rights reserved.