Balance between autocrine interleukin-1 beta and caspases defines life versus death of polymorphonuclear leukocytes

The role of endogenous IL-1 beta in regulating spontaneous and Fas-triggere d apoptosis of human PMN has been studied in relation to the activity of th e IL-1 beta -generating enzyme ICE (caspase-1), an enzyme also involved in the mechanism of cell death, Upon in vitro culture, PMN undergo spontaneous apoptosis and express increasing levels of IL-1 beta, caspase-1- and caspa se-3-like enzymes. Endogenous IL-1 beta protects PMN from apoptosis, since inhibition of either IL-1 beta or caspase-1 activity can accelerate PMN apo ptotic death. Thus, in spontaneous PMN apoptosis caspase-1 essentially play s an anti-apoptotic role by inducing maturation of protective IL-1 beta, wh ereas other molecules are responsible of driving apoptosis, Upon Fas trigge ring, PMN apoptosis is greatly accelerated, in correlation with increased c aspase activity, whereas IL-1 beta production is not augmented. Inhibition of IL-1 beta activity can increase Fas-induced apoptosis, whereas caspase-1 inhibitors are without significant effect, It is hypothesized that in Fas- induced PMN apoptosis caspase-1 has a double role: it can protect from apop tosis through generation of protective IL-1 beta, as in spontaneous apoptos is, and it can also exert pro-apoptotic activity which counterbalances the protective effect and allows accelerated apoptosis.