Induction and modulation of apoptosis in neonatal monocytes by polyunsaturated fatty acids

Abstract Polyunsaturated fatty acids (PUFAs), known modulators of the immune response, are the source of essential fatty acids in total parenteral nutrition–dependent patients. Critically ill infants on TPN have an increased incidence of sepsis, and lipid emulsions depress various immune functions. Recent studies have demonstrated that PUFAs induce apoptosis in various tissue cells in vitro and ex vivo. The susceptibility of neonatal monocytes, as major early effector cells in the host response to sepsis, to PUFA-mediated apoptosis and the mechanisms associated with PUFA-induced apoptosis were investigated. Both n-3 and n-6 PUFAs induced rapid, dose-dependent cell death in purified monocytes. Polyunsaturated fatty acids induced significant activation of upstream caspases 8 and 9 as well as caspase 3. The PUFA treatment resulted in a 4-fold increase in oxidative stress and a loss of monocyte mitochondrial potential compared with carrier controls ( P