The effect of salmeterol and salbutamol on mediator release and skin responses in immediate and late phase allergic cutaneous reactions

Background: Salmeterol is a long-acting beta(2)-agonist which in animal stu dies has been shown to possess antiinflammatory effects on early (EAR) and late (LPR) phase allergic responses. Purpose: To evaluate the anti-inflammatory effects of intradermally injecte d salmeterol and salbutamol on clinical and biochemical EAR and LPR in huma n skin. Methods: Measurement of wheal and flare reactions to allergen, codeine, and histamine, and LPR (induration) to allergen. Assessment of histamine and p rostaglandin D-2 (PGD(2)) release by microdialysis technique in EAR, and me asurement of mediators in LPR by suction blister technique. Results: Both beta(2)-agonists inhibited allergen-induced histamine release and wheal and flare reactions with maximum inhibition of 40-50% at 10(-6) M, a concentration which reduced PGD, synthesis by approximately 55%. Hista mine release by codeine and skin reactions to codeine and histamine were no t or only marginally reduced. Salmeterol and salbutamol (10(-6) M) inhibite d clinical LPR at 6 h by 71% and 48%, Except for the clinical LPR, no stati stical differences were found between the two drugs on any parameters. None of the drugs inhibited levels of histamine, tryptase, myeloperoxidase, or eosinophil cationic protein in LPR. Conclusions: Salmeterol and salbutamol inhibited allergen-induced skin resp onses, and reduced mediator release in EAR but not LPR. In general, the ant i-inflammatory effects of salmeterol did not differ from those induced by s albutamol.