Induction, distribution and modulation of upper airway allergic inflammation in mice

Background To further elucidate mechanisms of human allergic rhinosinusitis , we studied the induction, distribution and modulation of allergen-induced upper airway inflammation in a BALB/c mouse model. Methods Allergic inflammation induced with ovalbumin (OVA) by intraperitone al (IP) injection in alum was compared to repeated intranasal instillation. The type and distribution of inflammatory cells was compared in the respir atory and olfactory epithelial compartments. Eosinophil distribution was as sessed using Scarlet Red stain and a polyclonal antibody recognizing eosino phil major basic protein (MBP). The role of interleukin (IL)-5 in upper air way inflammation was tested by administration of polyclonal anti-IL-5 antib ody during the sensitization protocol. Results Unsensitized control mice receiving saline failed to develop upper airway eosinophil infiltration. IP OVA-sensitized mice developed marked upp er airway mucosal eosinophil infiltration after aerosol OVA challenge, wher eas repeated intranasal instillation of OVA produced qualitatively similar, but less intense eosinophil infiltration. Using either sensitization proto col, eosinophil infiltration was seen in areas of the lower portion of the nasal septum, the floor and the lower lateral walls of the mid-caudal regio n of the nasal cavity. Immunofluorescence staining for MBP confirmed this d istribution of eosinophils but also demonstrated some eosinophils in the ma xillary sinuses and in circumscribed regions of the ethmoturbinates. All ar eas of eosinophil infiltration were lined by respiratory epithelium. The se lective infiltration of respiratory but not olfactory epithelium by eosinop hils was unassociated with a measurable induction of epithelial ICA-M-1 or eotaxin expression. OVA-induced upper airway eosinophil infiltration was fo und to be IL-5 dependent, since administration of a polyclonal anti-IL-5 an tibody (TRFK-5) during OVA sensitization resulted in a marked modulation (8 0% decrease) in eosinophil infiltration in response to subsequent OVA chall enge. Conclusion The mouse upper airway, specifically in areas containing respira tory epithelium, is a target for OVA-induced allergic inflammation. This se lective infiltration of respiratory, but not olfactory, epithelium is, in p art, dependent upon IL-5. This model is useful for further dissection of th e inflammatory response with genetic manipulations and targeted immunologic al approaches.