Effects of local treatment with salmeterol and terbutaline on anti-IgE-induced wheal, flare, and late induration in human skin

The capacity of terbutaline and the long-acting β₂-agonist salmetcrol to suppress wheal-and-flare reactions (WFRs) to intradermal antihuman IgE and to histamine was evaluated in 36 healthy volunteers. We also exaniined effects of the two drugs on the subsequent late cutaneous reaction (LCR) to anti-IgE. Salmeterol (10^-10 10^-6 M) and terbutaline (10^-10 10^-5 M), injected intradermally 2 or 15 min before anti-IgE challenge, produced a dose-dependent inhibition of the WFRs to anti-IgE (liter 1:10000) with a maximal effect of ?60% (wheal) and ??75% (flare) by both drugs. On a molar basis, salmctcrol was approximately 10–100 times more potent than terbutaline in inhibiting the WFRs. Moreover, the wheal response to histamine (4 nmol) was antagonized by ?40% after prctrcatment with either salmeterol (10^-5 M) or terbutaline (10^-4 M). We found that both salmeterol and terbutaline exhibited anti-WFR activity for up to 24 h, salmeterol being significantly more potent in this regard. When selecting a 15-min pretreatment interval with equieffective anti-WFR doses from the first dose-response experiments (i.e., a salmetcrol: terbutaline ratio of 1:10), the WFRs to high-dose anti-IgE (titer 1:100) were inhibited by terbutaline (10^-5 M) by 25–30%, but not by salmeterol (10^-4). On the other hand. salmeterol attenuated (by up to ?35%) the subsequent LCR more effectively than terbutaline. As compared to the prctrcatment procedure, infiltration of the drugs (single doses) into the wheals 30 min after challenge with anti-IgE (titer 1:100) proved to be less effective on the development of LCRs. Taken together, salmeterol was found to express higher potency and have longer duration of action than terbutaline in inhibition of IgE-mediated inflammation in human skin.