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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Lung recruitment maneuvers (RMs), used to reopen atelectatic lung units and to improve oxygenation during mechanical ventilation, may result in hemodynamic impairment. We hypothesize that pulmonary arterial hypertension aggravates the consequences of RMs in the splanchnic circulation. Twelve anesthetized pigs underwent laparotomy and prolonged postoperative ventilation. ⋯ The corresponding recovery to at least 90% of baseline regional blood flow and organ perfusion lasted 1 to 5 min. Importantly, the decreases in regional blood flows and organ perfusion and the time to recovery of these flows did not differ from the controls. In conclusion, lipopolysaccharide-induced pulmonary arterial hypertension does not aggravate the RM-induced significant but short-lasting decreases in systemic, regional, and organ blood flows.
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Immature myeloid cells have been implicated as a source of postburn inflammation, and the appearance of these cells correlates with enhanced upregulation of hematopoiesis. The role of proliferative cells in postburn immune changes has not been directly tested. Gemcitabine, a ribonucleotide reductase inhibitor, has been shown to deplete proliferative immature myeloid cells in tumor models while sparing mature cells, leading to restored lymphocyte function and tumor regression. ⋯ Treatment of burn mice with gemcitabine ameliorated burn-induced susceptibility to LPS and infiltration of polymorphonuclear leukocytes into the liver and lung. Finally, gemcitabine treatment blocked the protective effect of burn injury upon P. aeruginosa infection. Our report shows that proliferative cells are major drivers of postburn immune changes and provides evidence that implicates immature myeloid cells in these processes.
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There is substantial evidence that gut barrier failure is associated with distant organ injury and systemic inflammation. After major trauma or stress, the factors and mechanisms involved in gut injury are unknown. Our primary hypothesis is that loss of the intestinal mucus layer will result in injury of the normal gut that is exacerbated by the presence of luminal pancreatic proteases. ⋯ Because comparable levels of gut injury caused by systemic insults are associated with gut-induced lung injury, which is mediated by biologically active factors in mesenteric lymph, we next tested whether this local model of gut injury would produce active mesenteric lymph or lead to lung injury. It did not, suggesting that gut injury by itself may not be sufficient to induce distant organ dysfunction. Therefore, loss of the intestinal mucus layer, especially in the presence of intraluminal pancreatic proteases, is sufficient to lead to injury and barrier dysfunction of the otherwise normal intestine but not to produce gut-induced distant organ dysfunction.
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Interleukin 22 (IL-22) is a TH17-like cytokine known to specifically activate epithelial cells, thereby strengthening immune defense at host/environment interfaces. Animal studies suggest that IL-22 may play a crucial role in clinical sepsis. However, little is known about IL-22 in sepsis patients. ⋯ Here, we report, for the first time, a modest but significant elevation of serum IL-22 detectable in abdominal sepsis patients (P G 0.001). Median serum concentrations of IL-22 were 111.8 pg/mL, 3.4 or 2.0 pg/mL, and 9.3 pg/mL for abdominal sepsis patients, surgical control patients (presurgery or postsurgery), and healthy volunteers,respectively. Interleukin 22 produced in the course of abdominal sepsis may contribute to host defense and stabilization of mucosal barrier functions under conditions of systemic infection.
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Diabetes mellitus is the leading comorbidity in patients with sepsis, but its impact upon survival and immunoinflammatory signaling in sepsis is undetermined. We investigated the effect of untreated diabetes mellitus upon survival and immunoinflammatory responses in the acute phase (days 1-5) of murine polymicrobial sepsis using the AKITA model of type 1 diabetes. Diabetic female C57BL/6-Ins2 (AKITA) and C57BL/6 wild-type (WT) mice underwent cecal ligation and puncture (CLP), blood (20 μL) was sampled for 5 days, and survival was monitored for 28 days. ⋯ A prelethal composite cytokine score was calculated on values obtained 24 h before death. This score was 3-fold lower for proinflammatory cytokines and 6-fold lower for anti-inflammatory mediators in the AKITA mice compared with the WT-Died mice but identical to the composite score in WT-Survived. These data demonstrate that untreated type I diabetes mellitus severely exacerbates sepsis mortality without inducing a prelethal release of systemic proinflammatory or anti-inflammatory cytokines.