Activation of nuclear factor κB in obstructive sleep apnea:: a pathway leading to systemic inflammation

Apnea-induced hypoxia and reoxygenation, which generates reactive oxygen species, may activate the oxidant-sensitive, proinflammatory transcription factor nuclear factor-kappa B (NF-kappa B), increasing systemic inflammation in obstructive sleep apnea. We measured NF-kappa B activity in circulating neutrophils and plasma levels of NF-kappa B-controlled gene products, soluble E (sE)-selectin and soluble vascular cell adhesion molecule-1 (sVCAM-1) in control subjects and in obstructive sleep apnea (OSA) patients. To confirm a causal link with OSA, we reassessed these parameters after nasal continuous positive airway pressure (CPAP) therapy. Twenty-two subjects undergoing evaluation for symptoms of sleep-disordered breathing were grouped by apnea hypopnea index: control, less than 5/h; mild to moderate OSA, 11-40/h; severe OSA, more than 40/h. A morning venous blood sample was obtained. Neutrophils were isolated, and NF-kappa B activity was determined by electrophoretic mobility shift assay. Plasma sE-selectin and sVCAM-1 were assayed by enzyme-linked immunosorbent assay. Neutrophils in mild to moderate and severe OSA patients showed 4.8-and 7.9-fold greater NF-kappa B binding activity compared with control subjects (p < 0.0001). The degree of NF-kappa B activation was positively correlated with indices of apnea severity. In five severe OSA patients, 1 month of CPAP therapy decreased neutrophil NF-kappa B activation to control levels. sE-selectin and sVCAM concentrations were reduced by CPAP in four of these five subjects. OSA leads to NF-kappa B activation, which may constitute an important pathway linking OSA with systemic inflammation and cardiovascular disease.