EFFECTS OF SALMETEROL AND TERBUTALINE ON IGE-MEDIATED DERMAL REACTIONS AND INFLAMMATORY EVENTS IN SKIN CHAMBERS IN ATOPIC PATIENTS

The objective of the present study was to investigate the potential of the long-acting beta(2)-agonist salmeterol as an inhibitor of various components of IgE-mediated inflammation in man. For this purpose, we measured gross skin reactivity (diameters of wheal and flare reaction [WFR] and late cutaneous reaction [LCR]) as well as inflammatory cells , mediators, and protein in cutaneous suction blister chambers in eigh t subjects with allergic rhinitis. Blisters were induced, two on each forearm, by gentle suction and heating, and were unroofed 12 h later, after which plastic chambers were placed over the denuded area. The ch ambers were challenged for 2 h with antihuman IgE (titer 1 : 10) in th e presence and absence of salmeterol or terbutaline. Normal goat IgG s erved as negative control. Chamber fluids were removed hourly for the first 4 h, and this was followed by a 4-h incubation before final coll ection. Salmeterol (10(-6) M) and terbutaline (10(-5) M) injected intr adermally 30 min before, as well as together with anti-IgE (titer 1 : 100), inhibited the WFRs by up to 30%. The effect of salmeterol on the ensuing LCR (75% inhibition at 24 h) tended to be more pronounced tha n the corresponding inhibition by terbutaline. Both salmeterol and ter butaline very effectively inhibited the anti-IgE-induced extravasation of alpha(2)-macroglobulin into skin chambers, with a significantly mo re sustained effect by salmeterol. Interestingly, only terbutaline red uced the histamine release evoked by anti-IgE. With the present experi mental design, where both drugs were washed out from the chambers afte r 2 h, neither drug inhibited recruitment of leukocytes (including eos inophils). Taken together, salmeterol had a more sustained inhibitory effect than terbutaline on indices of IgE-mediated edema formation (la te induration and plasma protein extravasation). On the other hand, un der the present experimental conditions, salmeterol failed to reduce t he histamine release (in contrast to terbutaline), and neither salmete rol nor terbutaline affected the recruitment of leukocytes.