Caspase-1-Dependent Pyroptosis of Peripheral Blood Mononuclear Cells Is Associated with the Severity and Mortality of Septic Patients

Abstract

Purpose. Pyroptosis has been known to play a vital role in the inflammation process which was induced by infection, injury, or inflammatory disease. The present study was aimed at evaluating the percentage of peripheral blood mononuclear cell (PBMC) pyroptosis in septic patients and assessing the correlation of PBMC pyroptosis with the severity and the mortality of septic patients. Methods. 128 trauma-induced patients with sepsis were enrolled in this prospective cohort study. Blood samples were collected, and PBMC pyroptosis was measured by flow cytometry within 24 hours after sepsis was diagnosed. Results. Percentage of PBMC pyroptosis was positively correlated with the acute physiology and chronic health evaluation (APACHE) II score and sequential organ failure assessment (SOFA) score (all P<0.01). The area under the curve (AUC) for the percentage of PBMC pyroptosis on a receiver operating characteristic curve was 0.79 (95% confidence interval (CI), 0.68–0.90). A Cox proportional hazard model identified an association between an increased percentage of PBMC pyroptosis (>14.17%) and increased risk of the 28-day mortality (hazard ratio=1.234, 95% CI, 1.014–1.502). Conclusion. The percentage of PBMC pyroptosis increases in septic patients, and the increased percentage of PBMC pyroptosis is associated with the severity of sepsis and the 28-day mortality of patients with sepsis.

Low-Density Granulocyte Contamination From Peripheral Blood Mononuclear Cells of Patients With Sepsis and How to Remove It – A Technical Report

“…This is an explanation for our observation, that the number of low-density granulocytes co-purifying with the PBMC fraction varies highly between patients. Although some of the studies depicting the problem of contaminating, co-purifying low-density granulocytes have been published a decade ago, it is still common practice today to use density gradient centrifugation for PBMC isolation from patients with sepsis (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33). This goes along with a lack of reported information on the isolation purity and identification of the contained cell types.…”

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

“…The complex clinical condition of sepsis may be best defined as the detrimental immunological host response to infection, leading to increased apoptosis of lymphoid and parenchymal tissues, immune suppression, and organ dysfunction 3 , 4 . Caspases may hold key-roles in sepsis in terms of apoptosis, pyroptosis, necroptosis, and inflammation 6 , 7 , 19 . In the present study, we showed for the first time that upregulated total apoptotic caspases in septic patients, including active and cleaved forms, are followed by anti-apoptotic hyperexpression, indicated by increased survivin serum levels, along with increased intracellular survivin transcript variants concentrations in early-onset sepsis.…”

Autophagy Regulation on Pyroptosis: Mechanism and Medical Implication in Sepsis

“…Pyroptosis is an ideal tool for the clearance of infected cells because it is a form of lytic cell death that causes release of abundant inflammatory cytokines and enables destruction of intracellular replicative niches. This might be the positive role of pyroptosis in infection, but if out of control, it could be detrimental to the host [21][22][23][24]. Pyroptosis contributes to the hyperinflammatory response in sepsis, and recent advances indicate its role in adaptive immunity, which is closely related to immune paralysis.…”