Am. J. Respir. Crit. Care Med., Vol 153, No. 2, Feb 1996, 576-581.
Beta 2-agonist treatment reduces beta 2-sensitivity in alveolar macrophages despite corticosteroid treatment
P Hjemdahl, A Zetterlund and K Larsson
Department of Clinical Pharmacology, Karolinska Hospital, Stockholm, Sweden.
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.
