Sustained high serum caspase-3 concentrations and mortality in septic patients

Abstract

Caspase-3 is the main executor of the apoptotic process. Higher serum caspase-3 concentrations in non-survivor compared to survivor septic patients have been found. The objectives of this work (with the increase of sample size to 308 patients, and the determination of serum caspase-3 concentrations also on days 4 and 8 of diagnosis of severe sepsis) were to know whether an association between serum caspase-3 concentrationss during the first week, degree of apoptosis, sepsis severity, and sepsis mortality exists. We collected serum samples of 308 patients with severe sepsis from eight intensive care units on days 1, 4 and 8 to measure concentrations of caspase-3 and caspase-cleaved cytokeratin (CCCK)-18 (to assess degree of apoptosis). End point was 30-day mortality. We found higher serum concentrations of caspase-3 and CCCK-18 in non-survivors compared to survivors on days 1 (p < 0.001), 4 (p < 0.001), and 8 (p < 0.001). We found an association between serum caspase-3 concentrations on days 1, 4 and 8 of severe sepsis diagnosis and serum CCCK-18 concentrations (p < 0.001), SOFA (p < 0.001), serum acid lactic concentrations (p < 0.001), and 30-day sepsis mortality (p < 0.001). The new findings of this work were that an association between serum caspase-3 concentrations during the first week, apoptosis degree, sepsis severity, and sepsis mortality exists.

Circulating biomarkers of mortality prediction in patients undergoing liver transplantation due to hepatocellular carcinoma

“…[98][99][100] In a study performed by our team with 145 patients with HCC undergoing LT, higher levels of caspase-3 in blood before LT were found in patients who died during the first year of LT than in survivors at 1 year. [101] These findings are in line with those of other studies reporting an association between high blood caspase-3 levels and an increased risk of mortality in patients with sepsis, [102] cerebral infarction, [103] traumatic brain injury [104] or cerebral hemorrhage. [105] The use of different agents decreased apoptosis and improved prognosis in animal models of sepsis, [106] traumatic brain injury, [107] cerebral infarction [108] and cerebral hemorrhage.…”

Survivin and caspases serum protein levels and survivin variants mRNA expression in sepsis

“…Similarly, higher caspase-3 activity has been found in lymphocytes of septic patients 26 , involved in brain hippocampal apoptosis in septic animal models 27 . An association of caspase-3 concentrations with sepsis severity, degree of apoptosis, and mortality in septic patients has recently been reported 28 . A caspase-dependent programmed neutrophil death (pyroptosis) associated with inflammation in sepsis is initiated by inflammasomes in innate immunity 29 .…”

Staphylococcus aureus Exploits the Host Apoptotic Pathway To Persist during Infection

“…For instance, CASP3 -inactivating SNPs, such as rs371145290 (c.653C→T, p.Ser218Leu), which predominantly occur in individuals of European ancestry, may hamper the development of abscesses as well as other staphylococcal diseases, such as endophthalmitis (45), necrotizing pneumonia (46), or mastitis (47), that have been shown to be associated with increased caspase-3 activity. Mortality rates in septic patients have also been shown to correlate with caspase-3 levels in human sera (48, 49). Thus, CASP3 variants with reduced apoptotic activity may also influence the outcome of life-threatening sepsis.…”