Inhibitory effects of inhaled flunisolide on inflammatory functions of alveolar macrophages

We have studied 15 patients with slight or moderate bronchial obstruction, all of whom were being treated by inhalation of the beta-mimetic fenoterol 4 x 400 micrograms/day, and 7 of whom were also receiving inhaled flunisolide 2 x 500 micrograms/day. The therapy had been given for longer than 1 month in each case. Bronchoscopy and bronchoalveolar lavage (BAL) was done for diagnosis or follow up of bronchial diseases. None of the patients showed signs of any interstitial lung disease. Conditioned culture supernatants were produced by cultivating alveolar macrophages (AM) for 24 h using standard conditions. To detect all the biological effects both of IL-1 alpha and IL-1 beta in the culture supernatants a modification of the standard mouse IL-1 thymocyte bioassay was used. The TNF concentration in culture supernatants was measured by ELISA. Free oxygen radical release by alveolar macrophages was determined by the detection of chemiluminescence. Both IL-1 and TNF production were significantly lower in patients receiving fenoterol plus flunisolide than in patients on fenoterol alone. In contrast, no difference could be observed in the release of free oxygen radicals from alveolar macrophages. Thus, for the first time an ex vivo study has revealed an interrelation between inhaled glucocorticoid therapy and inhibition of important mediators of inflammatory processes in the lower respiratory tract.