BETA(2)-AGONIST TREATMENT REDUCES BETA(2)-SENSITIVITY IN ALVEOLAR MACROPHAGES DESPITE CORTICOSTEROID TREATMENT

Alveolar macrophage beta(2)-adrenoceptor sensitivity and bronchodilato r 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 mu g twice a day by inhalation throu ghout the treatment period, and by giving 10 subjects 40 mg prednisolo ne and 10 subjects placebo orally 12 h before the second examination. Terbutaline treatment elicited marked attenuation (similar to 75% redu ctions) of isoprenaline-induced cyclic AMP accumulation in the alveola r macrophages. Responses to prostaglandin E(1) were not influenced by treatment, suggesting homologous beta-adrenoceptor desensitization. Co rticosteroid administration failed to either prevent (budesonide) or r everse (prednisolone) this desensitization. Bronchodilator responses t o terbutaline were not altered by treatment in either group. We conclu de that the beta(2)-adrenoceptor sensitivity of human alveolar macroph ages is markedly and selectively depressed by beta(2)-agonist treatmen t 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 uncle ar, but the present data in humans are of interest in relation to poss ible effects of continuous beta(2)-agonist treatment on inflammatory m echanisms in the airways.