NF-kappa B expression in mononuclear cells of patients with sepsis resembles that observed in lipopolysaccharide tolerance

The expression of NF-kappaB was studied in freshly isolated peripheral bloo d mononuclear cells (PBMC) of patients with severe sepsis and major trauma. The expression of p65p50 heterodimer, the active form of NF-kappaB, was si gnificantly reduced for all patients as compared with control subjects. The p50p50 homodimer, an inhibitory form of NF-kappaB, was reduced in the surv ivors of sepsis and in patients with trauma. Subsequent in vitro stimulatio n of PBMC with lipopolysaccharide (LPS) did not induce further NF-kappaB nu clear translocation: the survivors of sepsis and trauma patients showed low expression of both p65p50 and p50p50, whereas nonsurvivors of sepsis showe d a predominance of the inactive homodimer and a low p65p50/p50p50 ratio wh en compared with control subjects. In the later group of patients there was a reverse correlation between plasma IL-10 levels and the p65p50/p50p50 ra tio after in vitro LPS stimulation (r = -0.8, p = 0.04). The reduced expres sion of nuclear NF-kappaB was not due to its inhibition by I kappaB alpha, as very low expression of I kappaB alpha, as well as low levels of p65 and p50 were found in the cytoplasm of PBMC from patients with sepsis and traum a when compared with control subjects. These results demonstrate that upon LPS activation, PBMC of patients with systemic inflammatory response syndro me show patterns of NF-kappaB expression that resemble those reported durin g LPS tolerance: global down-regulation of NF-kappaB in survivors of sepsis and trauma patients and the presence of large amounts of the inactive homo dimer in the nonsurvivors of sepsis.