Nuclear Factor–κB and Its Role in Sepsis‐Associated Organ Failure

Abstract

Nuclear factor (NF)—κB is involved in regulating the transcription of many of the immunomodulatory mediators involved in the development of sepsis-induced organ failure. Kinase pathways involving p38 and Akt and initiated by engagement of Toll-like receptors modulate transcriptional activity of NF-κB, but apparently through different mechanisms. Increased activation of NF-κB occurs with sepsis, and greater levels of nuclear accumulation of NF-κB are associated with higher rates of mortality and worse clinical outcome. The percentage of apoptotic neutrophils is reduced in sepsis, and inhibition of nuclear translocation of NF-κB restores neutrophil apoptosis to baseline levels. In models of sepsis, suppression of NF-κB activation decreases acute inflammatory processes and organ dysfunction. Because NF-κB occupies a central role in signaling pathways important in sepsis, modulation of NF-κB activity may be an appropriate therapeutic target in patients with sepsis.