Inhibition of anti-IgE induced skin responsein normals by formoterol, a new β2-adrenoceptor agonist, and terbutaline

Formoterol, a new beta 2-selective long-acting bronchodilator, was compared with terbutaline in terms of ability to inhibit dual phase skin reactions to anti-human IgE in volunteers. Anti-IgE induced an early wheal and flare reaction (WFR) followed by a progressively increasing induration, the late phase reaction (LCR), lasting greater than or equal to 24 h. Intradermal injection of formoterol 20 ng or terbutaline 500 ng 5 min before challenge gave equal inhibition of the WFR. The subsequent LCR was suppressed by formoterol (30%) for the whole 24 h period, while terbutaline only attenuated the first 4 h period. Increasing the dose range of both drugs 25-fold, caused a further analogous reduction of the WFR to anti-IgE. In this higher dose range formoterol (0.5 micrograms) antagonized the following 1-24 h LCR by 50%, while terbutaline (25 micrograms) only attenuated the LCR by an average of 20%, with higher effect in the first 6 h period. The anti-LCR capacity of formoterol was highly superior to that of terbutaline (P less than 0.001). The histamine-elicited wheal response was attenuated by both drugs, but they had no effect on the flare response, favouring an anti-permeability action of both compounds. The data support the concept that terbutaline, given locally in a single dose shortly before challenge, inhibits the mast cell mediator release reaction with limited consequences for the following LCR. In contrast to terbutaline, formoterol exerted a substantial anti-LCR action, probably by interfering with inflammatory mechanisms after the initial mast cell mediator release.