The expression of
NF-kappaB was studied in freshly isolated peripheral blood mononuclear cells (PBMC) of patients with
severe sepsis and major
trauma. The expression of p65p50 heterodimer, the active form of
NF-kappaB, was significantly reduced for all patients as compared with control subjects. The p50p50 homodimer, an inhibitory form of
NF-kappaB, was reduced in the survivors of
sepsis and in patients with
trauma. Subsequent in vitro stimulation of PBMC with
lipopolysaccharide (LPS) did not induce further
NF-kappaB nuclear translocation: the survivors of
sepsis and
trauma patients showed low expression of both p65p50 and p50p50, whereas nonsurvivors of
sepsis showed a predominance of the inactive homodimer and a low p65p50/p50p50 ratio when compared with control subjects. In the later group of patients there was a reverse correlation between plasma
IL-10 levels and the p65p50/p50p50 ratio after in vitro LPS stimulation (r = -0.8, p = 0.04). The reduced expression of nuclear
NF-kappaB was not due to its inhibition by
IkappaBalpha, as very low expression of
IkappaBalpha, as well as low levels of p65 and p50 were found in the cytoplasm of PBMC from patients with
sepsis and
trauma when compared with control subjects. These results demonstrate that upon LPS activation, PBMC of patients with
systemic inflammatory response syndrome show patterns of
NF-kappaB expression that resemble those reported during LPS tolerance: global down-regulation of
NF-kappaB in survivors of
sepsis and
trauma patients and the presence of large amounts of the inactive homodimer in the nonsurvivors of
sepsis.