Blood neutrophil activation markers in severe asthma: lack of inhibition by prednisolone therapy

Bhupinder S Mann,Kian Fan Chung

doi:10.1186/1465-9921-7-59

Abstract

BackgroundNeutrophils are increased in the airways and in induced sputum of severe asthma patients. We determined the expression of activation markers from circulating neutrophils in severe asthma, and their supressibility by corticosteroids.MethodsWe compared blood neutrophils from mild, moderate-to-severe and severe steroid-dependent asthma, and non-asthmatics (n = 10 each). We examined the effect of adding or increasing oral prednisolone (30 mg/day;1 week).ResultsFlow cytometric expression of CD35 and CD11b, but not of CD62L or CD18, was increased in severe asthma. F-met-leu-phe increased CD11b, CD35 and CD18 and decreased CD62L expression in all groups, with a greater CD35 increase in severe asthma. In severe steroid-dependent asthma, an increase in prednisolone dose had no effect on neutrophil markers particularly CD62L, but reduced CD11b and CD62L on eosinophils. Phorbol myristate acetate-stimulated oxidative burst and IL-8 release by IL-1β, lipopolysaccharide and GM-CSF in whole blood from mild but not severe asthmatics were inhibited after prednisolone. There were no differences in myeloperoxidase or neutrophil elastase release from purified neutrophils.ConclusionBecause blood neutrophils in severe asthma are activated and are not inhibited by oral corticosteroids, they may be important in the pathogenesis of severe asthma.

Highlights

Neutrophils are increased in the airways and in induced sputum of severe asthma patients
The neutrophil may be an important inflammatory cell that contributes to the pathophysiology of severe asthma since increased neutrophilic inflammation measured in induced sputum and in the bronchial submucosa has been reported in such patients [5,6,7] Increased neutrophilic inflammation has been observed under other asthmatic circumstances
Stimulation of blood with FMLP increased the expression of CD11b, CD35, and CD18 surface molecules on gated neutrophils in all groups of patients; there was concomitantly a significant decrease in CD62L in all groups

Summary

Introduction

Neutrophils are increased in the airways and in induced sputum of severe asthma patients. A proportion of patients with asthma are not controlled and have persistent symptoms, recurrent exacerbations and/or persistent airflow obstruction despite using high doses of inhaled corticosteroids, and often oral corticosteroids, and long-acting β2-agonist bronchodilators [1]. This group of patients often termed severe asthma or therapy-resistant asthma forms a distinct category of asthma [2,3]. The neutrophil may be an important inflammatory cell that contributes to the pathophysiology of severe asthma since increased neutrophilic inflammation measured in induced sputum and in the bronchial submucosa has been reported in such patients [5,6,7] Increased neutrophilic inflammation has been observed under other asthmatic circumstances (page number not for citation purposes)

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Discussion

Conclusion