Transcription factor NF kappa B expression and postsurgical organ dysfunction

Objective To examine the role of neutrophil NF kappaB activation in organ dysfunction after major surgery. Summary Background Data NF kappaB is a transcription factor involved in the signal transduction of many stimuli that may participate in the pathogenesis of sepsis and resulta nt multiple organ dysfunction syndrome (MODS). It may therefore be a potent ial target for modulation in the reduction of postsurgical MODS. Methods Twenty-five patients undergoing major vascular surgery (thoracoabdominal ao rtic aneurysm repair) were studied. Perioperative levels of neutrophil NF k appaB, CD11b, and glutathione were measured. In vitro inhibition experiment s using NF kappaB inhibitors were also performed. Results No differences in clinical parameters were apparent before surgery between the patients who subsequently developed MODS and those who did not. However , there was a significant difference in preoperative levels of NF kappaB be tween the patients who developed postoperative organ dysfunction and those who did not. There was also a significant preoperative difference between p atients who survived surgery and those who did not. Glutathione levels were reduced both in patients who developed MODS and those who did not at the o nset of surgery. NF kappaB inhibitors suppressed patient plasma-stimulated NF kappaB activation in healthy neutrophils. Conclusions Preoperative neutrophil NF kappaB status may be a marker of postoperative o utcome after major surgery, and therapy aimed at attenuating neutrophil NF kappaB activation may reduce postoperative sepsis and organ dysfunction.