Abstract |
Background: Sepsis is a maladaptive inflammatory process in response to infectious agents, related to immune dysfunctions and devastating complications. Recently, interest has been shifted towards apoptotic (caspases) and antiapoptotic pathobiology (survivin protein), which might bring to light, attractive therapeutic interventions for septic intensive care unit (ICU) patients.
Methods: This prospective observational study was performed in a sample of critically ill pediatric patients (n=35) with sepsis, compared to patients with traumatic SIRS (n=35) and to healthy controls (n=30). The expression of survivin, was quantified through real-time quantitative polymerase chain reaction for the different survivin splice variants(WT, 2B, 3B and ΔΕx3). The apoptotic or antiapoptotic tendency was specified by measuring both the activity of survivin protein and caspases 3 and 9, through enzyme-linked immunosorbent assay method, according to the manufacturer’s instructions in serum samples.
Results: As far as the transcriptional behavior of survivin is concerned, survivin’s isoforms2B and ΔΕx3 were significantly higher in sepsis, compared to the SIRS group and controls (p<0.05), whereas survivin’s splice variant 3B tends to be depressed in sepsis. The enzymatic serum activity of survivin was highly expressed in sepsis, compared to SIRS and healthy controls (p<0.05). Finally, the caspases enzymatic study, especially of caspase 9 (p<0.05). also confirmed their upregulated activity in septic patients.
Conclusions: The upregulation of survivin and caspases 3 and 9 during the inflammatory process of sepsis is accompanied by the hyperexpression of isoforms of the antiapoptotic survivin protein. Specific apoptotic and antiapoptotic pathways might represent attractive targets for future research in the clarification of sepsis pathophysiology.
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