In vitro effect of beta 2-agonists on bacterial killing and superoxide anion (O2-) release from alveolar macrophages of patients with chronic bronchitis.
A new class of long-acting beta 2-adrenoceptor agonists has been studied in the last few years. Apparently, they display an important anti-inflammatory activity with an inhibition of different cellular functions. This study was carried out to compare a long-acting beta 2-agonist, formoterol, with a conventional short-acting one, salbutamol, on the release of superoxide anion (O2-) and bacterial killing by alveolar macrophages obtained with bronchoalveolar lavage (BAL) from 20 patients with chronic bronchitis. The O2- production in basal conditions was not affected by beta 2-agonists. On the contrary, after phagocytosis of opsonized zymosan 10(-5) M formoterol significantly affected the phagocytic index (difference between stimulated and basal O2- release): 7.9 +/- 2.0 nM O2-/10(6) AM/10 min vs 16.8 +/- 2.5, p < 0.0007. Bacterial killing was inhibited by the two drugs in a dose-dependent way, but the effect of formoterol was more evident than that of salbutamol. After blocking beta 2-receptors with propranolol, we observed a prevention of the beta 2-agonist effects on both O2- release and bacterial killing. The inhibition of the alveolar macrophage functions considered in this study is evident for both beta 2-agonists, but it is significantly more pronounced for formoterol. Our data can be interpreted as one possible mechanism of the anti-inflammatory effect described for long-acting beta 2-agonists. On the other hand, also a potential suppression of pulmonary antibacterial defenses must not be overlooked, particularly in chronic bronchitis, a disease characterized by recurrent airways infections. Whether current therapeutic dosages are sufficient to achieve anti-inflammatory or microbicidal suppressive effects of clinical relevance has not been demonstrated so far.
Capelli
A
A
Clinica del Lavoro Foundation, Veruno (NO), Italy.
Lusuardi
M
M
Carli
S
S
Zaccaria
S
S
Trombetta
N
N
Donner
C F
CF
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000368:Aged; D000420:Albuterol / Q000494:pharmacology*; D001991:Bronchitis / Q000503:physiopathology*; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000494:pharmacology*; D005260:Female; D000068759:Formoterol Fumarate; D006801:Humans; D066298:In Vitro Techniques; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011433:Propranolol / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D013481:Superoxides; D011433:Propranolol; D000420:Albuterol; D000068759:Formoterol Fumarate