CHARACTERIZATION OF A MURINE MODEL OF ALLERGIC PULMONARY INFLAMMATION

Pulmonary inflammation with eosinophil (EOs) infiltration is a promine nt feature of allergic respiratory diseases such as asthma. In order t o study the cellular response during the disease development, an anima l model of IgE-mediated pulmonary inflammation with characteristic eos inophilia is needed. We developed a method for inducing severe pulmona ry eosinophilia in the mouse and also studied the numbers of EOs in bl ood and bone marrow and the response to corticosteroid treatment. Anim als were sensitized with alum-precipitated ovalbumin (OVA) and challen ged with aerosolized OVA 12 days later when serum IgE levels were sign ificantly elevated. Four to eight hours after challenge there were mod erate increases in the number of EOs in the bone marrow and peripheral blood, but only a few EOs were observed in the lung tissue and in bro nchoalveolar lavage (BAL) fluid. Twenty-four hours after challenge, th ere was a marked reduction of EOs in bone marrow while the number of E Os peaked in the perivascular and peribronchial regions of the lung. F orty-eight hours after challenge, the highest number of EOs was found in the BAL fluid, making up >80% of all cells in that compartment. The high levels of EOs in the lung tissue and BAL fluid lasted for 2-3 da ys and was followed by a more moderate but persistent eosinophilia for another 10 days. Nonsensitized animals showed no significant changes in the number of EOs in BAL fluid, lungs, blood or bone marrow. Histop athological evaluation also revealed epithelial damage, excessive mucu s in the lumen and edema in the submucosa of the airways. The pulmonar y eosinophilia and decrease in bone marrow EOs induced by OVA challeng e responded well to treatment with several standard corticosteroids. T he rank order of steroid potency for inhibition of pulmonary eosinophi lia was betamethasone > prednisolone > hydrocortisone. Because mice ar e extremely useful for immunological studies, this model can be invalu able to study the effects of cytokines on pulmonary inflammation.