Lymphocyte Apoptosis, Caspase Activation and Inflammatory Response in Septic Shock

Abstract

We examined lymphocyte apoptosis, activity of caspases-1, -3, -8 and -9 and the relationship between those two events and inflammation response in septic shock. Blood samples were obtained within 24 h after diagnosis of septic shock from 16 patients to measure apoptosis, caspases-3, -8, -9 expression, changes in mitochondrial transmembrane potential and expression of Fas/FasL system of peripheral blood mononuclear cells (PBMCs). Moreover, serum levels of caspase-1 and blood concentrations of IL-6, IL-12, IL-15 and IL-18 were assessed. PBMCs from patients with septic shock compared to control individuals exhibited a greatly increased frequency of apoptosis (39.10 +/- 7.33% vs 4.19 +/- 1.13%; p < 0.001), an over expression of caspases-3, -8, and -9 (p < 0.01, p < 0.05, p < 0.001 for caspases-3, -8 and -9, respectively) as well as of Fas/FasL system (p < 0.05) and significant changes in mitochondrial transmembrane potential. Blood levels of caspase-1 (101.5 +/- 18.2 pg/ml vs 9.09 +/- 2.7 pg/ml, p < 0.001) and of IL-6, IL-12, IL-15 and IL-18 were significantly higher in septic patients vs control (p < 0.0001, p < 0.05, p < 0.05 and p < 0.0001, respectively). Furthermore, a correlation linking IL-6 blood level with both the apoptotic rate (r(2) = 0.75; p = 0.001) and caspase-9 expression (r(2) = 0.92; p = 0.0001) of PBMCs was observed.