title: Asthma therapy modulates priming-associated blood eosinophil responsiveness in allergic asthmatics.
abstract: Eosinophils play an important role in the pathogenesis of asthma. Several pro-inflammatory responses of eosinophils are primed in vivo in this disease. The aim of the present study was to investigate whether regular antiasthma treatment could modulate priming-sensitive cytotoxic mechanisms of human eosinophils. In a randomized, two-centre, double-blind parallel group study, the effect of 8 weeks of treatment with salmeterol xinafoate 50 microg b.i.d., beclomethasone dipropionate 400 microg b.i.d. or both on pulmonary function and the activation of priming-sensitive cytotoxic mechanisms of eosinophils, i.e. degranulation of eosinophil cationic protein (ECP) in serum, and activation of isolated eosinophils in the context of induction of the respiratory burst and release of platelet-activating factor (PAF) were tested. These effects were evaluated in 40 allergic asthmatics before and 24 h after allergen inhalation challenge. Whereas baseline forced expiratory volume in one second (FEV1) improved in all treatment groups, only treatment with a combination of salmeterol and beclomethasone significantly inhibited the allergen-induced increase in serum ECP, and (primed/unprimed) PAF-release, suggesting inhibition of eosinophil priming after allergen challenge. In contrast to the combination therapy, monotherapy with beclomethasone had no influence on allergen-induced PAF-release, suggesting an additional anti-inflammatory effect of salmeterol during combination therapy. Monotherapy with beclomethasone inhibited the prechallenge serum-treated zymosan (STZ) (0.1 mg mL(-1))-induced respiratory burst and the allergen-induced increase in serum ECP levels, reflecting pre- and postchallenge anti-inflammatory effects. During monotherapy with salmeterol, an allergen-induced increase in serum ECP concentration and STZ (0.1 mg x mL(-1))-induced respiratory burst was observed, suggesting that treatment with salmeterol alone had no effect on priming-sensitive eosinophil cytotoxic mechanisms. In conclusion, this study shows that standard asthma therapy leads to inhibition of eosinophil priming of cytotoxic mechanisms in vivo.
authors.affiliation: Dept of Pulmonary Diseases, Sint Antonius Hospital, Nieuwegein, The Netherlands.
authors.forename: J C
authors.initials: JC
authors.lastname: Grutters
authors.forename: L
authors.initials: L
authors.lastname: Brinkman
authors.forename: M M
authors.initials: MM
authors.lastname: Aslander
authors.forename: J M
authors.initials: JM
authors.lastname: van den Bosch
authors.forename: L
authors.initials: L
authors.lastname: Koenderman
authors.forename: J W
authors.initials: JW
authors.lastname: Lammers
mesh_terms: D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000328:Adult; D000420:Albuterol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000485:Allergens / Q000009:adverse effects*; D001249:Asthma / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D001507:Beclomethasone / Q000627:therapeutic use*; D001798:Blood Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D001985:Bronchial Provocation Tests; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D010972:Platelet Activating Factor / Q000096:biosynthesis / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects; D012260:Ribonucleases; D000068299:Salmeterol Xinafoate; D016896:Treatment Outcome; D015054:Zymosan
chemical_list: D000318:Adrenergic beta-Agonists; D000485:Allergens; D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D005938:Glucocorticoids; D010972:Platelet Activating Factor; D017382:Reactive Oxygen Species; D000068299:Salmeterol Xinafoate; D015054:Zymosan; D012260:Ribonucleases; D001507:Beclomethasone; D000420:Albuterol