title: Caspase-3 activation, Bcl-2 contents, and soluble FAS-ligand are not related to the inflammatory marker profile in patients with sepsis and septic shock.
abstract: The current comparative investigation analyses markers of inflammation and apoptosis in peripheral blood of intensive care unit (ICU) patients with postoperative/posttraumatic SIRS (systemic inflammatory response syndrome), sepsis, severe sepsis, or septic shock. Inflammatory markers (C-reactive protein [CRP], cytokines, metalloproteinases [MMPs]) and soluble FAS-Ligand (sCD178) were determined in plasma, and apoptosis-relevant antigens such as active caspase-3, Bcl-2, and sCD178 were quantified in whole-blood cell lysates. These parameters were analyzed daily in 20 postoperative/posttraumatic patients: 2 patients had SIRS, 5 suffered from sepsis (2 died), and 13 had septic shock (5 died). Active caspase-3, Bcl-2, and sCD178 were determined by ELISA and by fluorescence-activated cell sorting (FACS)-array kits using bead-assisted flow cytometry. Cytokines and MMPs were quantified by Luminex-assisted Beadlyte assays. Active caspase-3 was identified in defined samples of whole-blood lysates covering, for example, 5/7, 8/18, and 6/11 consecutive days during the patients' stay on the ICU. Also, sCD178 was detected on successive days. Peaks of active caspase-3 antigen contents in whole blood occurred independently of CRP and inflammatory cytokines such as tumor necrosis factor (TNF)-alpha and IL-6. In addition, high MMPs 1-3, 7-10, and 13 concentrations were detected. Interestingly, active caspase-3 and cell-associated sCD178 were either elevated simultaneously or in a close time window. The same was true for Bcl-2. In conclusion, activation of apoptosis can be determined in whole blood of postoperative/posttraumatic patients by active caspase-3 and by Bcl-2. Pro- and antiapoptotic effects during sepsis may occur independently of peaks in inflammatory markers. Apoptosis could explain modeling and remodeling of leukocyte subpopulations.
authors: Department of Experimental Anesthesiology, University Clinic Ulm, Steinhoevelstrasse 9, 89075 Ulm, Germany.
authors: Fabian
authors: F
authors: Kriebel
authors: Silke
authors: S
authors: Wittemann
authors: Hsin-Yun
authors: HY
authors: Hsu
authors: Thomas
authors: T
authors: Joos
authors: Manfred
authors: M
authors: Weiss
authors: E Marion
authors: EM
authors: Schneider
mesh_terms: D053148:Caspase 3 / Q000378:metabolism*; D004789:Enzyme Activation; D053222:Fas Ligand Protein / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D018805:Sepsis / Q000201:enzymology / Q000378:metabolism*; D012772:Shock, Septic / Q000201:enzymology / Q000378:metabolism*
chemical_list: D053222:Fas Ligand Protein; D018836:Inflammation Mediators; D019253:Proto-Oncogene Proteins c-bcl-2; D053148:Caspase 3