Abraham Edward
Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
J Infect Dis. 2003 Jun 15;187 Suppl 2:S364-9. doi: 10.1086/374750.
Nuclear factor (NF)-kappaB 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-kappaB, but apparently through different mechanisms. Increased activation of NF-kappaB occurs with sepsis, and greater levels of nuclear accumulation of NF-kappaB 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-kappaB restores neutrophil apoptosis to baseline levels. In models of sepsis, suppression of NF-kappaB activation decreases acute inflammatory processes and organ dysfunction. Because NF-kappaB occupies a central role in signaling pathways important in sepsis, modulation of NF-kappaB activity may be an appropriate therapeutic target in patients with sepsis.
核因子（NF）-κB参与调节许多与脓毒症诱导的器官功能衰竭发生相关的免疫调节介质的转录。涉及p38和Akt且由Toll样受体激活引发的激酶途径可调节NF-κB的转录活性，但显然是通过不同机制。脓毒症时NF-κB的激活增加，且NF-κB核内积聚水平越高，死亡率越高，临床结局越差。脓毒症时凋亡中性粒细胞的百分比降低，抑制NF-κB的核转位可使中性粒细胞凋亡恢复至基线水平。在脓毒症模型中，抑制NF-κB激活可减轻急性炎症过程和器官功能障碍。由于NF-κB在脓毒症重要的信号通路中占据核心地位，调节NF-κB活性可能是脓毒症患者合适的治疗靶点。
