Major basic protein and eosinophil-derived neurotoxin concentrations in nasal-lavage fluid after antigen challenge: Effect of systemic corticosteroids and relationship to eosinophil influx

The late-phase response to nasal challenge with antigen is associated with a mixed inflammatory cell influx in which the eosinophil demonstrates the earliest and greatest proportionate rise. We investigated the evidence for activation of the eosinophil during the late response by measuring the concentration of the eosinophil-derived mediator major basic protein (MBP) and the eosinophil-derived neurotoxin (EDN) in nasal-lavage fluids before and for 11 hours after antigen challenge in 13 subjects with seasonal allergic rhinitis. The subjects received oral prednisone (20 mg three times daily) or placebo in a double-blind, crossover manner for 2 days before each of two antigen challenges. After placebo pretreatment, significant increases over diluent baseline (4.5 ± 0.4 ng/ml) occurred in the levels of MBP in nasal-lavage fluid during the early (9.8 ± 2.9 ng/ml; p < 0.005) and late (15.3 ± 4.8 ng/ml; p < 0.01) responses to antigen challenge. Significant increases (p < 0.05) in the concentration of EDN also occurred during the late response to antigen that correlated with the levels of MBP (r = 0.48; p < 0.001). The cumulative late-phase increase in MBP correlated closely (r_s = 0.96; p < 0.005) with the total influx of eosinophils. Oral prednisone pretreatment significantly reduced the mean of each subject's peak late-phase concentration of both MBP (30.7 ± 5.8 ng/ml versus 13.3 ± 4.3 ng/ml; p = 0.005) and EDN (885 ± 659 ng/ml versus 71 ± 41 ng/ml; p < 0.05). These data provide evidence for eosinophil degranulation during the late response and inhibition of this response by prednisone, supporting its pathogenetic role.