Lymphocyte apoptosis, caspase activation and inflammatory response in septic shock.
BACKGROUND
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.


METHODS
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.


RESULTS
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.
Delogu
G
G
Famularo
G
G
Tellan
G
G
Marandola
M
M
Antonucci
A
A
Signore
M
M
Marcellini
S
S
Moretti
S
S
D017209:Apoptosis; D020169:Caspases / Q000097:blood*; D016207:Cytokines / Q000097:blood*; D053222:Fas Ligand Protein / Q000097:blood; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D012772:Shock, Septic / Q000097:blood / Q000201:enzymology* / Q000276:immunology*; D019014:fas Receptor / Q000097:blood
D016207:Cytokines; C491901:FAS protein, human; D053222:Fas Ligand Protein; D019014:fas Receptor; D020169:Caspases