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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Bradykinin (BK) is regarded as an important mediator of edema, shock, and inflammation during sepsis. In this study, we evaluated the contribution of BK in porcine sepsis by blocking BK and by measuring the stable BK metabolite, BK1-5, using anesthetized pigs. The effect of BK alone, the efficacy of icatibant to block this effect, and the recovery of BK measured as plasma BK1-5 were first investigated. ⋯ In conclusion, icatibant completely blocked the hemodynamic effects of BK but had no beneficial effects on N. meningitidis-induced edema, shock, and inflammation. This and the fact that plasma BK1-5 in all the septic pigs was virtually nondetectable question the role of BK as an important mediator of porcine sepsis. Thus, the data challenge the current view of the role of BK also in human sepsis.
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Dietary lipids/cholesterol may modulate liver immune function. We have recently found that mouse F4/80 Kupffer cells are classified into phagocytic CD68 Kupffer cells and cytokine-producing CD11b Kupffer cells. We here investigate how a high-fat and/or high-cholesterol diet affects innate immune liver mononuclear cells. ⋯ Although the proportion of CD68 Kupffer cells decreased in HFCD mice, phagocytic activity of them was enhanced. Mice fed with HCD rather than those fed with HFD showed features closer to HFCD mice. Thus, enhanced function of mouse liver mononuclear cells is likely dependent on the liver cholesterol level, rather than the liver triglyceride level.
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Previous animal and human studies have suggested that total plasma sulfide plays a role in the pathophysiology of shock. This study's aim was to determine the value of total plasma sulfide as a marker of shock severity in nonsurgical adult patients admitted to the ICU. Forty-one patients, with various types of shock (septic, cardiogenic, obstructive, and hypovolemic), were included in the study, with an average total plasma sulfide concentration of 23.2 ± 26.3 µM. ⋯ Area under the receiver operating characteristic for total plasma sulfide as a predictor of ICU mortality was 0.739 (confidence interval, 0.587-0.892; P = 0.009). Even after correcting for APACHE II score and lactate values, total plasma sulfide correlated with mortality (odds ratio, 1.058; 95% confidence interval, 1.001-1.118; P = 0.045). The study provides evidence that, in nonsurgical adult ICU patients admitted because of any type of shock, total plasma sulfide correlates with administered norepinephrine dose at admission, severity of disease (APACHE II score ≥30 points), and survival outcome.
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Sepsis is characterized by systemic inflammation with release of a large amount of inflammatory mediators. If sustained, this inflammatory response can lead to multiple organ failure and/or immunoparalysis. In the latter condition, the host may be susceptible to opportunistic infections or be unable to clear existing infections. ⋯ It also suggests that LXA4 reduced systemic inflammation and NF-κB activation without compromising host defense. Increased macrophage recruitment was in part due to a direct effect of LXA4 as LXA4 increased peritoneal macrophage recruitment in sham controls and partly due to reduced production of IL-10 as LXA4 decreased macrophage IL-10 release (a known inhibitor of macrophage migration) after CLP. The results suggest that LXA4 increased survival in sepsis by simultaneously reducing systemic inflammation as well as bacterial spread.