Nuclear factor kappa B: a pivotal role in the systemic inflammatory response syndrome and new target for therapy.
NF-kappaB is an important transcription factor complex that appears to play a fundamental role in regulating acute inflammation through activation of the cytokine cascade and production of other pro-inflammatory mediators. There is increasing evidence that NF-kappaB is important in the pathobiology of disease states such as SIRS, MODS and ARDS; therefore, therapeutic interventions aimed at limiting NF-kappaB activation and down-regulating production of inflammatory mediators could prove to be beneficial in decreasing host-derived tissue injury and organ dysfunction. Specific interventions that hold promise for suppressing NF-kappaB activation include the use of antioxidants, inhibition of NIK and the IKK signalsome, treatment with proteasome inhibitors, induction of endotoxin tolerance and, possibly the use of corticosteroids in selected patients.
Christman
J W
JW
Department of Medicine, Vanderbilt University School of Medicine and the Department of Veterans Affairs, Nashville, TN 37322-2650, USA. john.christman@mcmail.vanderbilt.edu
Lancaster
L H
LH
Blackwell
T S
TS
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D015815:Cell Adhesion Molecules / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D006023:Glycoproteins / Q000627:therapeutic use; D006801:Humans; D051550:I-kappa B Kinase; D007378:Interleukins / Q000276:immunology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000276:immunology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D013256:Steroids; D018746:Systemic Inflammatory Response Syndrome / Q000150:complications / Q000188:drug therapy* / Q000276:immunology*
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015815:Cell Adhesion Molecules; D016207:Cytokines; D006023:Glycoproteins; D007378:Interleukins; D016328:NF-kappa B; D013256:Steroids; C039304:calpain inhibitors; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human