Tumour necrosis factor-alpha production in human alveolar macrophages: modulation by inhaled corticosteroid

Using an ex vivo alveolar macrophage model, the hypothesis that inhaled pre parations of corticosteroids might have important anti-inflammatory effects on cells of the peripheral airway was tested. The tumour necrosis factor (TNF)-alpha-inducing potential of three glycolip id preparations from nonpathogenic (arabinofuranasyl lipoarabinomannan (LAM (Ara-LAM)) and virulent (mannase LAM (ManLAM)) mycobacteria and Cram-negat ive bacteria (lipopolysaccharide (LPS)), in primary alveolar macrophage pre parations was investigated, A novel inhaled chlorofluorocarbon (CFC)-free p reparation of beclomethasone dipropionate (hydrofluoroalkane 134a (HFA)-BDP ) with increased peripheral lung deposition was investigated for its abilit y to modulate glycolipid-induced TNF-alpha production by human alveolar mac rophages, in comparison with a CFC-containing preparation and placebo. Compared to the basal TNF-alpha bioactivity of 0.72 ng.mL(-1) (geometric me an), the TNF-alpha bioactivity in the macrophage preparation increased foll owing incubation with LPS (138 ng.mL(-1),p<0.001), AraLAM (12.6 ng.mL(-1), p<0.001) and ManLAM (1.42 ng.mL(-1), p=0.02), HFA-BDP, administered in vivo , significantly reduced LPS- and ManLAM-induced TNF-alpha production by alv eolar macrophages cultured cr vivo. No change in glycolipid-induced TNF-alp ha production was observed following in vivo administration of CFC-BDP or H FA-placebo, This is the first demonstration of an immunomodulatory effect on alveolar c ells of corticosteroid delivered via metered dose inhaler. The present find ings suggest that alveolar deposition of beclomethasone dipropionate is cap able of modulating the inflammatory potential of the alveolar macrophage po pulation.