Inhibition of anti-IgE induced skin response in normals by formoterol, a new beta 2-adrenoceptor agonist, and terbutaline. 2. Effect on the late phase reaction.
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.
Grönneberg
R
R
Department of Lung Medicine, Huddinge University Hospital, Sweden.
Zetterström
O
O
D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D000068759:Formoterol Fumarate; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology*; D007271:Injections, Intradermal; D008297:Male; D008407:Mast Cells; D008875:Middle Aged; D011897:Random Allocation; D011943:Receptors, Adrenergic, beta / Q000008:administration & dosage / Q000494:pharmacology*; D012867:Skin / Q000276:immunology*; D013726:Terbutaline / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D000888:Antibodies, Anti-Idiotypic; D004983:Ethanolamines; D011943:Receptors, Adrenergic, beta; D007073:Immunoglobulin E; D013726:Terbutaline; D000068759:Formoterol Fumarate