Dose and time dependent effects of caffeine on superoxide release, cell survival and DNA fragmentation of alveolar macrophages from rat lung

In this study, the effect of two concentration ranges of the cAMP phosphodi esterase inhibitor, caffeine, on alveolar macrophage function was investiga ted by measuring survival rate, superoxide anion production and DNA fragmen tation. 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 prod uction 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 a nd diphenylamine reaction, was obtained for 3 and 24 h of culture. The effe ct of caffeine on survival rate was also time dependent. At low caffeine co ncentrations, 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 k illed a fraction of the population. The results suggest that low concentrat ions of caffeine prevent apoptosis of macrophages, whereas at moderate conc entrations caffeine induces apoptosis in these cells. The results are discu ssed in relation to the mechanism of cAMP. (C) 2000 Elsevier Science Irelan d Ltd. All rights reserved.