Eosinophil activation status and corticosteroid responsiveness in severe asthma

Background: Since eosinophils are implicated in asthma pathogenesis, we inv estigated whether these cells were activated in severe asthma. Methods: Twe nty-six asthmatics with different clinical responses to oral corticosteroid (CS), i.e. sensitive [change in forced expiratory volume in 1 s (Delta FEV 1) greater than or equal to 25% after oral methylprednisolone, 40 mg daily, for 14 days, n = 7], resistant (Delta FEV1 less than or equal to 15%, n = 9) and dependent (greater than or equal to 20 mg oral prednisone daily for acceptable asthma control, n = 10), were studied. Results: Calcium ionophor e-induced leukotriene (LT) C-4 release of purified blood eosinophils was si milar in the three groups. Cell incubation with granulocyte-macrophage colo ny-stimulating factor (GM-CSF) enhanced ionophore-induced LTC4 release, and this effect was higher in CS-sensitive (5-fold) than in CS-resistant subje cts (1.7-fold) (p = 0.02). CS treatment decreased blood eosinophil counts i n these two groups of subjects (p less than or equal to 0.02) and decreased GM-CSF-enhanced LTC4 release in CS-sensitive asthmatics only (p = 0.04). i n contrast, despite a high mean daily dose of oral CS (35 +/- 8 mg), blood counts of eosinophils from CS-dependent subjects were higher(p = 0.03) and GM-CSF enhancement of LTC4 release was greater (2.8-fold) than in CS-sensit ive (2.1-fold) and CS-resistant (1.7-fold) subjects (p = 0.04). Interesting ly, serum from CS-resistant subjects reduced GMCSF enhancement of LTC4 rele ase by eosinophils of CS-sensitive asthmatics (p = 0.001). Conclusions: Eos inophils from CS-dependent asthmatics have an impaired response to CS, wher eas serum from CS-resistant subjects contains an inhibitor of eosinophil re sponse to GMCSF. Copyright (C) 2000 S. Karger AG, Basel.