Increased nuclear factor kappa B activation in critically ill patients who die

Objectives: To determine nuclear factor kappa B (NF kappa B) activation in mononuclear and neutrophils from critically ill patients and to compare NF kappa B activation with circulating concentrations of interleukin (IL)-6, IL-8, and soluble intercellular adhesion molecule (sICAM)-1.

Design: Observational study.

Setting: University Teaching Hospital, eight-bed intensive care unit in northeast Scotland.

Patients: Ten patients admitted to the intensive care unit who fulfilled the criteria for systemic inflammatory response syndrome were studied at 0, 24, 48, and 72 hrs. Six healthy volunteers were also studied.

Interventions: None.

Measurements and Main Results: NF kappa B activation was significantly higher in patients compared to healthy volunteers in both neutrophils (p =.001) and mononuclear leukocytes (p =.013). In the six patients who survived to 96 hrs, the level of NF kappa B activation in mononuclear cells remained constant (p =.9). However, in the four patients who died before 96 hrs, mononuclear cell NF kappa B activation increased markedly and was significantly higher before death than in those who survived to 96 hrs (p =.0105). NF kappa B activation in neutrophils similarly remained constant in patients who survived to 96 hrs (p =.4) but did not show the same increase before death. Circulating concentrations of IL-6, IL-8, and sICAM-1 were elevated but were unrelated to leukocyte NF kappa B activation.

Conclusions: We found NF kappa B activation in mononuclear and neutrophils in patients with systemic inflammatory response syndrome, which increased markedly before death in mononuclear leukocytes and was not related to plasma IL-6, IL-8, and sICAM-1 concentrations. These data support the need for further study of the role of NF kappa B activation in mortality from systemic inflammatory response syndrome and sepsis.