Allergen-induced murine upper airway inflammation: local and systemic changes in murine experimental allergic rhinitis

The role of inflammatory effector cells in the pathogenesis of airway aller gy has been the subject of much investigation. However, whether systemic fa ctors are involved in the development of local responses in both upper and lower airways has not been fully clarified. The present study was performed to investigate aspects of the pathogenesis of isolated allergic rhinitis i n a murine model sensitized to ovalbumin (OVA). Both upper- and lower-airwa y physiological responsiveness and inflammatory changes were assessed, as w ell as bone marrow progenitor responses, by culture and immunohistological methods. Significant nasal symptoms and hyper-responsiveness appeared after intranasal OVA challenge (P < 0.0001 and P < 0.01, respectively), accompan ied with significant nasal mucosal changes in CD4(+) cells (P < 0.001), int erleukin (IL)-4(+) cells (P < 0.01), IL-5(+) cells (P < 0.01), basophilic c ells (P < 0.02) and eosinophils (P < 0.001), in the complete absence of hyp er-responsiveness or inflammatory changes in the lower airway. In the bone marrow, there were significant increases in CD34(+) cells, as well as in eo sinophils and basophilic cells. In the presence in vitro of mouse recombina nt IL-5, IL-3 or granulocyte-macrophage colony-stimulating factor (GM-CSF), the level of bone marrow eosinophil/basophil (Eo/Baso) colony-forming cell s increased significantly in the OVA-sensitized group. We conclude that, in this murine model of allergic rhinitis, haemopoietic progenitors are upreg ulated, which is consistent with the involvement of bone marrow in the path ogenesis of nasal mucosal inflammation. Both local and systemic events, ini tiated in response to allergen provocation, may be required for the pathoge nesis of allergic rhinitis. Understanding these events and their regulation could provide new therapeutic targets for rhinitis and asthma.