INVOLVEMENT OF IL-5 IN A MURINE MODEL OF ALLERGIC PULMONARY INFLAMMATION - PROPHYLACTIC AND THERAPEUTIC EFFECT OF AN ANTI-IL-5 ANTIBODY

Interleukin-5 (IL-5) is important in the control of differentiation, m igration, and activation of eosinophils. In order to study the role of IL-5 in the development of eosinophilic inflammation of the airways, we have used a monoclonal antibody to murine IL-5 (TRFK-5) in a murine model of allergic pulmonary inflammation. BSD2F1 mice were sensitized with alum-precipitated ovalbumin and were challenged with aerosolized ovalbumin on day 12 after sensitization. Samples of bronchoalveolar l avage (BAL) fluid, lung tissue, blood, and bone marrow aspirate were c ollected at different times after ovalbumin challenge. Twenty-four hou rs after challenge there were significant increases in the number of e osinophils in the BAL fluid, lung tissue, and blood while bone marrow eosinophils were decreased. Treatment of sensitized mice with TRFK-5 ( 0.01-1 mg/kg, i.p.) 2 h before ovalbumin challenge reduced the numbers of eosinophils in the BAL fluid and lung tissue and prevented the dec rease in bone marrow eosinophils in a dose-dependent fashion. The numb er of eosinophils in the BAL fluid, peribronchial and alveolar regions of the lung was also reduced when TRFK-5 (2 mg/kg, i.p.) was given up to 5 d after ovalbumin challenge. Furthermore, there was no evidence of increased epithelial damage, edema, or the presence of mucus that c ould have resulted from eosinophil apoptosis and release of toxic prot eins after neutralization of IL-5. These results demonstrate an import ant role for IL-5 in the development of eosinophilic inflammation of t he airways and for the migration of eosinophils from the bone marrow i nto blood in response to antigen challenge. In addition, our results i ndicate that inhibitors of IL-5 should be therapeutically effective wh en administered during an established eosinophilic inflammation of the lung.