INDUCTION, DURATION, AND RESOLUTION OF AIRWAY GOBLET CELL HYPERPLASIAIN A MURINE MODEL OF ATOPIC ASTHMA - EFFECT OF CONCURRENT INFECTION WITH RESPIRATORY SYNCYTIAL VIRUS AND RESPONSE TO DEXAMETHASONE

We recently described a murine model of atopic asthma in which a marke d, extensive hyperplasia of airway goblet cells is induced by repeated challenge of ovalbumin (OA)-sensitized mice with intratracheally admi nistered allergen (Am. J. Respir. Cell Mol. Biol. 1996;14:425-438). We report here the time course of the duration of this feature and of it s spontaneous resolution in the absence of further allergen exposure. Induction of severe neutrophilic inflammation in the airways by repeat ed intratracheal administration of lipopolysaccharide failed to induce goblet cell hyperplasia (GCH) to as great a degree as that induced by allergen, suggesting that nonallergic inflammation is a relatively po or inducer of this phenotype change in mice. When a ''subclinical'' in fection of the lungs with the human A2 strain of respiratory syncytial virus was superimposed on the model of atopic asthma, recruitment of monocytes and lymphocytes to the airways was enhanced and a discharge of goblet cell mucin contents was observed. This may partly explain th e respiratory difficulty that typifies virally induced exacerbations o f asthma in humans. Daily systemic treatment of sensitized mice with d examethasone during the period of allergen challenge produced a dose-r elated suppression of developing GCH, while similar treatment during t he period following the establishment of extensive hyperplasia induced an accelerated resolution toward a normal epithelial phenotype. These results confirm and extend the relevance of this model as a represent ation of the human disease.