The immuno-inflammatory host response in critically ill patients with sepsis and inflammatory conditions is driven by the expression of compounds acting as, or producing inflammatory mediators, including cytokines, reactive oxygen species and adhesion molecules. Their production is in part controlled by the transcription factor, nuclear factor <span style='font-family: Symbol'>kB (NF<span style='font-family:Symbol'>kB). NF<span style='font-family:Symbol'>kB is a primary intracellular transcription factor, which transduces extracellular signals to the nucleus and responds to cellular oxidative stress. NF<span style='font-family:Symbol'>kB activation was assessed in circulating leucocytes from critically ill patients on the intensive care unit. NF<span style='font-family:Symbol'>kB was activated in mononuclear and polymorphonuclear leucocytes in all the patients studied, and was significantly greater than in healthy subjects (p=0.01, p=0.001). NF<span style='font-family:Symbol'>kB activation in mononuclear leucocytes increased markedly in those patients who died whilst remaining constant in those patients who survived. The effect of administration of the intracellular antioxidant N-acetylcysteine, on NF<span style='font-family:Symbol'>kB activation and circulating concentrations of cytokines and adhesion molecules was investigated in patients with sepsis. In patients who survived and received N-acetylocysteine, mononuclear leucocyte NF<span style='font-family:Symbol'>kB activation decreased significantly (p=0.016). In contrast there was no change in NF<span style='font-family:Symbol'>kB activation in mononuclear leucocytes from patients who received the placebo infusion. Additionally, circulating concentrations of interleukin (IL)-8 were found to decrease in those surviving patients receiving N-acetylcysteine. The effect of IL-10 on NF<span style='font-family:Symbol'>kB activation, coupled to 1<span style='font-family:Symbol'>kB<span style='font-family:Symbol'>a degradation, in leucocytes and tissues in endotoxaemic rats, was investigated. NF<span style='font-family:Symbol'>kB activation was increased with a corresponding reduction in 1<span style='font-family:Symbol'>kB<span style='font-family:Symbol'>a concentrations, in liver (p=0.02) and lung (p=0.004) samples from rats receiving combined LPS and IL-10. NF<span style='font-family:Symbol'>kB activation may have a central role in the mortality and sepsis. N-acetylcysteine attenuates mononuclear leucocyte NF<span style='font-family:Symbol'>kB activation and related IL-8 production in human sepsis, whereas, IL-10 administration resulted in paradoxical increases in NF<span style='font-family:Symbol'>kB activation.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:288273 |
| Date | January 2002 |
| Creators | Paterson, Ross L. |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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