Circulating eosinophil/basophil progenitors and nasal mucosal cytokines in seasonal allergic rhinitis.

Accumulation of eosinophils in the airways is characteristic of allergic rhinitis and asthma. The tissue eosinophilia may involve both recruitment of mature eosinophils and proliferation of their progenitors. This study examines mature eosinophils (nasal and circulating), their circulating progenitors, and a potential role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in stimulating these progenitors. Twelve subjects with a history of seasonal allergic rhinitis and positive skin prick test for birch pollen were studied during four periods: shortly before, in the early and intense phase, at the end, and well after the Swedish birch-pollen season. Nasal mucosal and circulating eosinophils were examined in both nasal brushings and peripheral blood samples. Eosinophil/ basophil progenitors were determined by counting colony-forming units in nonadherent mononuclear blood-cell cultures in methylcellulose at 14 days. The nasal mucosal cytokines GM-CSF, interleukin (II)-1 beta, IL-3, IL-5, IL-6, IL-8, and RANTES were analyzed (ELISA) in nasal ravage (NAL) fluids. All patients developed severe symptoms of rhinitis at the height of the season, with increased numbers of eosinophils in the nasal mucosa (P<0.05) and in the circulation (P<0.05). At this time point, the number of circulating progenitors (P<0.05) and the NAL fluid level of CM-CSF (P<0.05) were also increased. In contrast, there was no change in the NAL fluid levels of IL-1 beta, IL-3, IL-6, or IL-8. Neither IL-5 nor RANTES could be detected in any of the NAL fluids. At the end of or after the season, there was no increase in nasal eosinophils or circulating eosinophils or progenitors (P>0.05). Ex vivo addition of GM-CSF (10-100 U) increased the number of blood progenitors grown before (P<0.01) and after (P<0.05) the season, compared with during the season. The in vitro GM-CSF responsiveness of progenitors may be related to whether or not these already have been stimulated endogenously by GM-CSF. Taken together, our data thus suggest that GM-CSF may play a role in vivo to increase production of eosinophilic progenitors in allergic airway disease.