Abstract

In this study, the effect of two concentration ranges of the cAMP phosphodiesterase inhibitor, caffeine, on alveolar macrophage function was investigated by measuring survival rate, superoxide anion production and DNA fragmentation. The results show caffeine induced apoptosis in alveolar macrophages in a dose dependent manner. The survival rate of the cells exposed to low concentrations of caffeine (< 5 mM) increased remarkably with a peak at 2.5 mM. At this concentration, caffeine failed to affect superoxide anion production and DNA degradation. However, at higher concentrations (5-20 mM), at which the viability was higher than the control, a significant increase in both superoxide production and DNA degradation, as judged by agarose gel and diphenylamine reaction, was obtained for 3 and 24 h of culture. The effect of caffeine on survival rate was also time dependent. At low caffeine concentrations, macrophages survived with a viability of 90-97 after 3 days. At moderate concentrations, the cells maintained viability up to 24 h but at concentrations higher than 20 mM, caffeine inhibited cell survival and killed a fraction of the population. The results suggest that low concentrations of caffeine prevent apoptosis of macrophages, whereas at moderate concentrations caffeine induces apoptosis in these cells. The results are discussed in relation to the mechanism of cAMP. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.