Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Comparative Study
Predictive value of monocyte histocompatibility leukocyte antigen-DR expression and plasma interleukin-4 and -10 levels in critically ill patients with sepsis.
It has been suggested that excessive activation of the anti-inflammatory pathways in sepsis may lead to poor outcome of patients with sepsis. The aim of this study was to test the value of histocompatibility leukocyte antigen (HLA)-DR-expression on blood monocytes and plasma levels of interleukin (IL)-4 and -10 in prediction of hospital mortality in patients with sepsis. Sixty-one critically ill patients with sepsis were prospectively enrolled to this study in two university hospital intensive care units. ⋯ Only IL-10 levels on days 1 and 2 showed reasonable predictive power (AUCs 0.706 and 0.725, respectively). The highest AUC values were those of APACHE-II (0.786) and admission SOFA score (0.763). In conclusion, APACHE II and SOFA scores on admission showed better discriminatory power than HLA-DR expression and IL-10 and IL-4 levels in prediction of hospital mortality in critically ill patients with sepsis.
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We recently reported that hypothermia protects against intrapulmonary nitric oxide overproduction and nitric oxide-mediated lung injury in endotoxemic rats. Few studies have been performed to investigate whether hypothermia reduces inflammation by affecting favorable changes in chemokine and pro- and anti-inflammatory cytokine profiles. In this study, we tested the hypothesis that hypothermia decreases concentrations of growth-related oncogene/cytokine-induced neutrophil chemoattractant-1 (GRO/CINC-1), interleukin (IL)-1beta, IL-6, and myeloperoxidase and increases concentration of IL-10 in the lungs endotoxemic rats. ⋯ Hypothermia inhibits neutrophil recruitment in the lungs of endotoxemic rats in part by decreasing proinflammatory cytokine expression. Additionally, hypothermia induces intrapulmonary IL-10 expression. Further studies are needed to investigate whether IL-10 mediates the anti-inflammatory effects of hypothermia.
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Some anesthetics attenuate expression of endotoxin-induced production of proinflammatory genes. The anesthetic combination of ketamine/xylazine (K/X) decreases lipopolysaccharide (LPS)-induced liver injury in rats. However, the effects of K/X on gut function and gene expression are unknown. ⋯ These data indicate that K/X inhibits some proinflammatory genes and pathophysiologic responses in the serum and stomach during endotoxemia. The effects of K/X appear to inhibit transcriptional events in iNOS expression, which may be dependent on K/X-induced inhibition of early TNF-alpha expression. Furthermore, in rat models of endotoxemia, especially those evaluating the stomach, careful consideration needs to be given if anesthetic combinations with ketamine and/or xylazine are used, as they alter LPS-induced responses.
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The protective effects and roles of AT1-receptor antagonists (AT1-RA) or angiotensin-converting enzyme inhibitors (ACEI) on vascular endothelial cell (EC) injury during hypoxia are not entirely known. Therefore, we investigated these effects and mechanisms in human aortic (HA) EC. DNA fragmentation, Lactate dehydrogenase (LDH) release, and caspase-3 activity were measured in cultured HAEC after exposure to hypoxia in the presence or absence of an AT1-RA (candesartan, CS) and/or an ACEI (temocaprilat, TC). ⋯ This effect was attenuated by the kinin B2 receptor antagonist, HOE 140, and the NOS inhibitor, N-nitro-L-arginine methylester (L-NMMA). Hypoxia activates the pathway leading to apoptosis by enhancing caspase-3 activity. Both CS and TC can ameliorate hypoxia-induced apoptosis in HAEC through inhibiting caspase-3 activation by enhancing ecNOS activity, via the accumulation of BK.
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A mouse model of burn injury demonstrates increasing mortality to an infectious challenge in the form of cecal ligation and puncture (CLP) reaching a peak at 10 days after injury. Because it is widely believed that peritoneal mast cells play an important role in the defense against peritoneal sepsis, we wished to explore the possibility that peritoneal mast cell dysfunction contributed to increased CLP mortality after burn injury. Kit(W-v) C57BL/6 mice, which were shown to lack peritoneal mast cells by cytospin and flow cytometry, and normal littermate control animals were subjected to 25% burn or sham burn injury and 10 days later underwent CLP. ⋯ A study of peritoneal cell populations 24 h after CLP failed to reveal an obvious cause for the difference in CLP survival between the two mast cell-deficient strains. Tumor necrosis factor-alpha (TNF-alpha) measurements in peritoneal fluid showed appreciable amounts of TNF-alpha in the littermate controls of both strains and little in the fluid obtained from the mast cell-deficient animals of both strains. We conclude that peritoneal mast cell dysfunction is unlikely to be a major cause of decreased resistance to peritoneal sepsis in burn-injured animals and that the importance of peritoneal mast cells in combating peritoneal sepsis in the mouse appears to be strain dependent.