The neonatal 'sepsis redox cycle'. IL6 and IL8 activate NF-κB, resulting in increased inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. IL6 and IL8 also activate NADPH oxidase. iNOS produces large amounts of nitric oxide (·NO), which inhibits the electron transport chain (ETC), leading to increased mitochondrial superoxide (·O2-) production. COX-2 and NADPH oxidase produce cytoplasmic ·O2-, where it is dismutated by CuZn superoxide dismutase (SOD) to H2O2. In mitochondria, ·O2- may react with ·NO from cytoplasm to produce peroxynitrite (ONOO-), which is protonated to ONOOH and further decomposed to ·OH and ·NO2. Alternatively, ·O2- is dismutated by MnSOD. If not degraded by GSH peroxidase (GPx), H2O2 leaks from mitochondria. H2O2 strongly activates NF-κB, thus closing and further promoting the redox loop. Mitochondria with an inhibited electron transport chain and damaged by ·OH and ·NO2 produce less ATP, which leads to energy depletion and cellular dysfunction. sIL6R, soluble IL6 receptor; IL8R, IL8 receptor.