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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Cardiopulmonary bypass (CPB) is associated with immune paresis, which predisposes to the development of postoperative sepsis. The aims of this study were to characterize the ex vivo cytokine responses to bacterial cell wall components in whole blood from patients undergoing CPB and to determine whether altered leukocyte expression of Toll-like receptors (TLRs) is involved in immune paresis after CPB. We recruited 6 patients undergoing routine cardiac surgery with CPB. ⋯ At the end of CPB, there was more than 50% reduction in neutrophil TLR2 and TLR4 expression (P < 0.05), with recovery to baseline the following day. There was a 29% reduction in monocyte TLR4 expression at the end of CPB (P < 0.05) and more than 120% increase in monocyte TLR2 and 4 expression the following day (P < 0.05). In conclusion, reduced ex vivo production of cytokines cannot be fully accounted for by downregulation of TLR expression, although receptor upregulation may contribute to the later recovery of responsiveness.
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The present study was undertaken to determine whether the mice depleted of alphabeta or gammadelta T cells show resistance to acute polymicrobial sepsis caused by cecal ligation and puncture (CLP). T-cell receptor beta knockout (betaTCRKO) and T-cell receptor delta knockout (deltaTCRKO) mice were used. An additional group of mice was treated with an antibody against the alphabeta T-cell receptor to induce alphabeta T-cell depletion; a subset of alphabeta T cell-deficient mice was also treated with anti-asialoGM1 to deplete natural killer (NK) cells. ⋯ These studies indicate that mice depleted of alphabeta but not of gammadelta T cells are resistant to mortality in an acutely lethal model of CLP. The depletion of NK cells caused further survival benefit in alphabeta T cell-deficient mice. These findings suggest that alphabeta T and NK cells mediate or facilitate CLP-induced inflammatory injury.
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Macrophage migration inhibitory factor (MIF) is a mediator of innate immunity and important in the pathogenesis of septic shock. Lipopolysaccharide (LPS) and tumor necrosis factor (TNF) alpha are reported to be inducers of MIF. We studied MIF and cytokines in vivo in patients with meningococcal disease, in human experimental endotoxemia, and in whole blood cultures using a newly developed sensitive and specific enzyme-linked immunosorbent assay. ⋯ MIF was not detected in blood in experimental endotoxemia, nor after stimulation of whole blood with LPS or meningococci, although high levels of TNF-alpha were seen in both models. In conclusion, MIF is increased in patients with meningococcal disease and highest in the presence of shock. Macrophage migration inhibitory factor cannot be detected in a human endotoxemia model and is not produced by whole blood cells incubated with LPS or meningococci.
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Peritonitis represents a procoagulant state because of activated coagulation and inhibited fibrinolysis. Intra-abdominal fibrin deposition-entrapping bacteria-prevents bacterial spread but impairs bacterial clearance. Activating intra-abdominal fibrinolysis by recombinant tissue-type plasminogen activator (r-tPA) early during peritonitis may enhance bacterial clearance and reduce inflammation. ⋯ Survival rate was not affected by any dose of r-tPA lavage compared with saline lavage. Delayed local stimulation of fibrinolysis by peritoneal r-tPA lavage enhanced intra-abdominal bacterial clearance and reduced intra- and extra-abdominal coagulation responses in a dose-dependent manner. Survival rate was unaffected likely due to adverse changes in IL-12 and IL-10 levels.
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The aim of this study was to investigate whether the type of i.v. fluid administered has an impact on outcome in an animal model of septic shock. The study included 28 anesthetized, invasively monitored, mechanically ventilated female sheep (29.5 +/- 4.0 kg), which received 0.5 g/kg body weight of feces into the abdominal cavity to induce peritonitis. During the surgical operation and 4 h after feces spillage, only Ringer's lactate (RL) was administered in all animals. ⋯ Blood interleukin (IL) 6 concentrations were significantly increased in all groups. The mean survival time was similar in all groups. In this clinically relevant model of prolonged septic shock, albumin and HES solution resulted in higher cardiac output, oxygen delivery, and lower blood lactate levels than gelatin and RL; however, the choice of i.v. fluid did not affect outcome.