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 beta2-adrenoceptor agonists has been studie d in the last few years. Apparently, they display an important anti-in flammatory activity with an inhibition of different cellular functions . This study was carried out to compare a long-acting beta2-agonist, f ormoterol, with a conventional short-acting one, salbutamol, on the re lease of superoxide anion (O2-) and bacterial killing by alveolar macr ophages obtained with bronchoalveolar lavage (BAL) from 20 patients wi th chronic bronchitis. The O2- production in basal conditions was not affected by beta2-agonists. On the contrary, after phagocytosis of ops onized zymosan 10(-5) M formoterol significantly affected the phagocyt ic 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 kill ing was inhibited by the two drugs in a dose-dependent way, but the ef fect of formoterol was more evident than that of salbutamol. After blo cking beta2-receptors with propranolol, we observed a prevention of th e O2-agonist effects on both O2- release and bacterial killing. The in hibition of the alveolar macrophage functions considered in this study is evident for both 132-agonists, but it is significantly more pronou nced for formoterol. Our data can be interpreted as one possible mecha nism of the anti-inflammatory effect described for long-acting beta2-a gonists. 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-inf lammatory or microbicidal suppressive effects of clinical relevance ha s not been demonstrated so far.