Eosinophils and eosinophil cationic protein in nasal lavages in allergen-induced hyperresponsiveness: effects of topical glucocorticosteroid treatment

Abstract

Airway challenges with allergen are frequently followed by an increase in responsiveness to both specific and unspecific stimuli. This phenomenon in the lower airways has been linked to the presence of a late phase response to allergen challenge. One of the hallmarks of the late phase response is a tissue infiltration of granulocytes, specifically the eosinophils. A hypothesis for the increase in responsiveness has been that local activation of these eosinophils with subsequent release of the toxic granular constituents leads to a decrease in the barrier function of the airway epithelium. The aim of the present study was to further explore this hypothesis. Ten patients with previously demonstrated nasal allergen-induced hyperresponsiveness participated in a double-blind cross-over study involving pretreatment for various periods with topical glucocorticosteroids. The patients were challenged intranasally with allergen on one day, rechallenge 24 h later and the increase in responsiveness noted. In a nasal lavage performed immediately prior to challenge the number of eosinophilic granulocytes and the level of eosinophilic cationic protein (ECP) was determined. As expected, the placebo-treated patients demonstrated an increase in nasal responsiveness at rechallenge accompanied by a tendency for an increase in eosinophils as well as ECP in the lavage preceding the rechallenge compared with the initial allergen challenge 24 h previously. The amount of ECP found in the lavage on the second day correlated with the TAME-esterase activity, a marker of ongoing inflammatory activity (r = 0.64; P < 0.05) in the same lavage, suggesting participation of the eosinophilic granulocyte in the inflammatory response to allergen. However, there were no correlations between number of eosinophils or ECP content in the nasal lavages on the first or second day and the degree of the increased responsiveness obtained on the second day. Further, topical treatment with glucocorticosteroids, which totally abolished the increased responsiveness, did not appear to significantly change the levels of ECP in the nasal lavage prior to the initial or re-challenge. It is therefore suggested that the increase in responsiveness seen after an airway allergen challenge is not only a result of eosinophil activation but is a more complex phenomenon.