In vitro effect of beta 2-agonists on bacterial killing and superoxide anion (O2-) release from alveolar macrophages of patients with chronic bronchitis

Chest. 1993 Aug;104(2):481-6. doi: 10.1378/chest.104.2.481.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Adrenergic beta-Agonists / pharmacology*
  • Aged
  • Albuterol / pharmacology*
  • Bronchitis / physiopathology*
  • Chronic Disease
  • Dose-Response Relationship, Drug
  • Ethanolamines / pharmacology*
  • Female
  • Formoterol Fumarate
  • Humans
  • In Vitro Techniques
  • Macrophages, Alveolar / drug effects
  • Macrophages, Alveolar / physiology*
  • Male
  • Middle Aged
  • Propranolol / pharmacology
  • Staphylococcus aureus / physiology*
  • Superoxides / metabolism*

Substances

  • Adrenergic beta-Agonists
  • Ethanolamines
  • Superoxides
  • Propranolol
  • Albuterol
  • Formoterol Fumarate