Beta 2-agonist treatment reduces beta 2-sensitivity in alveolar macrophages despite corticosteroid treatment.
Alveolar macrophage beta 2-adrenoceptor sensitivity and bronchodilator responses to inhaled terbutaline were investigated before and after 2 wk of oral treatment with terbutaline 7.5 mg twice a day in healthy volunteers. The influence of corticosteroid treatment was examined by giving 10 subjects budesonide 400 micrograms twice a day by inhalation throughout the treatment period, and by giving 10 subjects 40 mg prednisolone and 10 subjects placebo orally 12 h before the second examination. Terbutaline treatment elicited marked attenuation (approximately 75% reductions) of isoprenaline-induced cyclic AMP accumulation in the alveolar macrophages. Responses to prostaglandin E1 were not influenced by treatment, suggesting homologous beta-adrenoceptor desensitization. Corticosteroid administration failed to either prevent (budesonide) or reverse (prednisolone) this desensitization. Bronchodilator responses to terbutaline were not altered by treatment in either group. We conclude that the beta 2-adrenoceptor sensitivity of human alveolar macrophages is markedly and selectively depressed by beta 2-agonist treatment and that corticosteroid treatment, contrary to previous hypotheses, fails to influence this phenomenon. Studies on the mechanisms involved are needed. The importance of alveolar macrophages in asthma is unclear, but the present data in humans are of interest in relation to possible effects of continuous beta 2-agonist treatment on inflammatory mechanisms in the airways.
Hjemdahl
P
P
Department of Clinical Pharmacology, Karolinska Hospital, Stockholm, Sweden.
Zetterlund
A
A
Larsson
K
K
D000280:Administration, Inhalation; D000284:Administration, Oral; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D000527:Alprostadil / Q000494:pharmacology; D019819:Budesonide; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage / Q000494:pharmacology; D011282:Pregnenediones / Q000008:administration & dosage / Q000494:pharmacology; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects* / Q000378:metabolism; D015656:Respiratory Mechanics / Q000187:drug effects; D016037:Single-Blind Method; D013147:Spirometry; D013726:Terbutaline / Q000008:administration & dosage / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D005938:Glucocorticoids; D011282:Pregnenediones; D018343:Receptors, Adrenergic, beta-2; D019819:Budesonide; D011239:Prednisolone; D000242:Cyclic AMP; D000527:Alprostadil; D007545:Isoproterenol; D013726:Terbutaline