Nuclear factor-κB and its role in sepsis-associated organ failure

被引:192
作者
Abraham, E [1 ]
机构
[1] Univ Colorado, Hlth Sci Ctr, Div Pulm Sci & Crit Care Med, Denver, CO 80262 USA
关键词
D O I
10.1086/374750
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:S364 / S369
页数:6
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