Asthma therapy modulates priming-associated blood eosinophil responsiveness in allergic asthmatics

Eosinophils play an important role in the pathogenesis of asthma. Several p ro-inflammatory responses of eosinophils are primed in vivo in this disease . The aim of the present study was to investigate whether regular antiasthm a 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 mu g b.i.d, beclometha sone dipropionate 400 mu g b.t.d. or both on pulmonary function and the act ivation of priming-sensitive cytotolic mechanisms of eosinophils, ie. degra nulation of eosinophil cationic protein (ECP) in serum, and activation of i solated eosinophils in the contest of induction of the respiratory burst an d release of platelet-activating factor (PAF)) were tested. These effects w ere evaluated in 40 allergic asthmatics before and 24 h after allergen inha lation challenge. Whereas baseline forced expiratory volume in one second (FEV1) improved in all treatment groups, only treatment with a combination of salmeterol and b eclomethasone significantly inhibited the allergen-induced increase in seru m ECP, and (primed/unprimed) PAF-release, suggesting inhibition of eosinoph il priming after allergen challenge. In contrast to the combination therapy , monotherapy,vith beclomethasone had no influence on allergen-induced PAF- release, suggesting an additional antiinflammatory effect of salmeterol dur ing combination therapy, Monotherapy with beclomethasone inhibited the prec hallenge serum-treated zymosan (STZ) (0.1 mg mL(-1)-induced respiratory bur st and the allergen-induced increase in serum ECP levels, reflecting pre- a nd postchallenge anti-inflammatory effects. During monotherapy,vith salmete rol, an allergen-induced increase in serum ECP concentration and STZ (0.1 m g.mL(-1))-induced respiratory burst was observed, suggesting that treatment with salmeterol alone had no effect on priming-sensitive eosinophil cytoto xic mechanisms. In conclusion, this study shows that standard asthma therapy leads to inhib ition of eosinophil priming of cytotoxic mechanisms in vivo.