Cytokines suppress apoptosis independent of increases in reactive oxygen levels.

Antioxidants suppress apoptosis induced by diverse stimuli in many cells, including immune cells, suggesting that reactive oxygen species (ROS) are common mediators of apoptosis. We evaluated the potential role for ROS in the apoptosis of myeloid progenitors following withdrawal of survival factors and in the apoptosis triggered by enforced c-myc expression, two model systems of programmed cell death. ROS are potential mediators of these cell deaths, as low concentrations of H2O2 (0.1-0.2 mM) or menadione (less than = 10 microM) induced myeloid cell apoptosis, and cytokines effectively suppressed this cell death. Apoptosis following IL-3 withdrawal and c-Myc-induced cell death was also effectively suppressed by the antioxidants pyrrolidine dithiocarbamate and glutathione peroxidase. Moreover, measurements of intracellular ROS in cells treated with oxidants or antioxidants showed a correlation between levels of reactive oxygen and the induction or suppression of apoptosis. However, apoptosis following IL-3 withdrawal and c-Myc-induced cell death was not associated with increased reactive oxygen. Therefore, myeloid programmed cell death is not associated with increases in ROS.