Superoxide generation by alveolar macrophages from aged rats: improvement by in vitro treatment with IFN-gamma

Alveolar macrophages (AM) from aged rats show an impaired oxidative response, but it is unclear whether or not this is due to the inability of these cells to be activated. To elucidate this, we investigated the capacity of AM from young (16-week-old) and aged (100-week-old) rats to become primed with recombinant rat interferon-gamma (IFN-gamma) for increased phorbol myristate acetate (PMA)-elicited O2- production, utilizing an MCLA-dependent chemiluminescent assay. We also compared concanavalin A- or Bacillus Calmette Guerin (BCG)-induced IFN-gamma production by the spleen cells of young and aged animals. The data indicated that AM freshly harvested from non-sensitized aged rats produced less O2- than those from young animals. A similar result was obtained in BCG-sensitized rats. However, AM from aged rats were primed with in vitro treatment with IFN-gamma for increased rate of O2- production to an equivalent level of that by AM from young animals. In addition, the ability of spleen cells to produce IFN-gamma was well maintained in aged rats. These results suggest that AM function is suppressed in the lungs of aged animals. Our observation that the decreased AM function in aged rats can be reversed is important because it suggests that appropriate treatment may reduce the incidence and mortality of respiratory infections in the elderly.