Relationship between Plasma Levels of Lipopolysaccharide (LPS) and LPS‐Binding Protein in Patients with Severe Sepsis and Septic Shock

Opal, Steven M.; Scannon, Patrick J.; Vincent, Jean‐Louis; White, Mark L.; Carroll, Stephen F.; Palardy, John E.; Parejo, Nicolas A.; Pribble, John P.; Lemke, Jon H.

doi:10.1086/315093

Cited by 537 publications

(429 citation statements)

References 37 publications

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“…However, at present, the treatment for sepsis using MSCs is focused more on the inhibition of the excessive inflammatory reaction caused by sepsis, and the effect of MSCs on the immune system remain to be fully elucidated. As lipopolysaccharide (LPS) is the predominant compound promoting the involvement of Gram-negative bacteria in sepsis, and the severity of sepsis is correlated with the concentration of LPS in the circulatory system (12,13), LPS is commonly injected into an animal model in order to simulate sepsis.…”

Section: Introductionmentioning

confidence: 99%

Effects of bone marrow mesenchymal stem cells on the cardiac function and immune system of mice with endotoxemia

Zhou

et al. 2016

Molecular Medicine Reports

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Abstract. The present study aimed to investigate the effects of bone marrow mesenchymal stem cells (MSCs) on the cardiac function and immune system of mice with endotoxemia. The mice were divided into the following groups: Control group, endotoxemia group, lipopolysaccharide (LPS) treatment group, LPS and MSC treatment group (LPS + MSC group) and MSC group. Following treatment with LPS, the cardiac function of the mice was examined at after 2, 6 and 24 h, and on day 7. An enzyme-linked immunofluorescent assay was used to analyze the serum and the levels of cytokines in the myocardium, and western blotting was used to investigate any changes in the levels of signaling proteins associated with the myocardium. A 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay was used to investigate the growth rate of the splenic cells at after 24 h and on day 7, and the humoral immune function and phagocytosis of the macrophages in the mice were also examined. The cardiac function of the mice with endotoxemia declined, although this impairment was circumvented following treatment with MSCs. The levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α and IL-10 in the serum and the myocardium increased following stimulation by LPS, although these declined as a result of MSC treatment. The expression levels of Toll-like receptor 4, p65-nuclear factor-κB and phosphorylated p38 in the mouse myocardium were enhanced following stimulation by LPS, which subsequently decreased as a result of MSC treatment. Compared with the control group, the growth rate of the splenic cells, humoral immune function and the level of phagocytosis of macrophages were all increased, although these parameters declined following treatment with MSCs. Taken together, the present study revealed that the MSCs inhibited the inflammatory reaction in the mice with endotoxemia, and improved cardiac function. By contrast, the cellular and humoral immunity were depressed, and phagocytosis of the macrophages, which were enhanced following simulation with LPS, were decreased following treatment with MSCs. However, no overexpression of the anti-inflammatory factor, IL-10, was observed. The present study hypothesized that MSCs exert a bifunctional role in endotoxemia, by inhibiting inflammatory factors, including IL-1 and IL-6, and inhibiting the compensatory expression of IL-10 following LPS stimulation. This avoids the possibility of excessive inhibition of immunological function, as this results in immunosuppression, and a higher ratio of IL-10 to TNF-α is indicative of a poor prognosis in patients with sepsis.

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Section: Introductionmentioning

confidence: 99%

Effects of bone marrow mesenchymal stem cells on the cardiac function and immune system of mice with endotoxemia

Zhou

et al. 2016

Molecular Medicine Reports

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“…4 Bacterial endotoxin or lipopolysaccharides (LPSs), major components of the outer cell membrane of Gramnegative bacteria, are principal mediators in the pathophysiology of sepsis. 7 LPSs induce their noxious effects by interaction with CD14-bearing inflammatory cells, which include monocytes-macrophages, neutrophils and other non-immune cells. 8 These effector cells appear to be activated through TLR-4 and subsequently release a plethora of pro-inflammatory cytokines, including TNFa, interleukin (IL)-1b, IL-8, IL-12, cyclic endoperoxides, platelet activating factor (PAF), complement, tissue factor and other harmful mediators, which contribute to the induction of the systemic inflammatory response syndrome.…”

Section: Introductionmentioning

confidence: 99%

“…8 These effector cells appear to be activated through TLR-4 and subsequently release a plethora of pro-inflammatory cytokines, including TNFa, interleukin (IL)-1b, IL-8, IL-12, cyclic endoperoxides, platelet activating factor (PAF), complement, tissue factor and other harmful mediators, which contribute to the induction of the systemic inflammatory response syndrome. [7][8][9] Under the above cited circumstances, the liver is a fundamental organ involved in LPS detoxification and, therefore, in the following sections, experimental and clinical aspects related to the liver function, during and after LPS exposure, will be illustrated.…”

Section: Introductionmentioning

confidence: 99%

Review: The role of the liver in the response to LPS: experimental and clinical findings

Jirillo

Caccavo

Magrone

et al. 2002

Journal of Endotoxin Research

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The liver plays an important physiological role in lipopolysaccharide (LPS) detoxification and, in particular, hepatocytes are involved in the clearance of endotoxin of intestinal derivation. In experimental shock models, tumor necrosis factor (TNF)-a induces hepatocyte apoptosis and lethal effects are due to secreted TNF-a and not to cell-associated TNF-a. An exaggerated production of TNF-a has been reported in murine viral infections, in which mice become sensitized to low amounts of LPS and both interferon (IFN)-g and IFN-a/b are involved in the macrophage-induced release of TNF-a. The prominent role of LPS and TNF-a in liver injury is also supported by studies of ethanol-induced hepatic damage. In humans, evidence of LPS-induced hepatic injury has been reported in cirrhosis, autoimmune hepatitis, and primary biliary cirrhosis and a decreased phagocytic activity of the reticulo-endothelial system has been found in these diseases. The origin of endotoxemia in hepatitis C virus (HCV) infected patients seems to be multifactorial and LPS may be of exogenous or endogenous derivation. In endotoxemic HCV-positive patients responsive to a combined treatment with IFN-a/ribavirin (RIB), endotoxemia was no longer detected at the end of the therapeutic regimen. By contrast, 48% of the non-responders to this treatment were still endotoxemic and their monocytes displayed higher intracellular TNF-a and interleukin (IL)-1b levels than responders. Moreover, in responders, an equilibrium between IFN-g and IL-10 serum levels was attained. In the non-responders, serum levels of IL-10 did not increase following treatment. This may imply that an imbalance between T helper (Th) 1 and Th 2 derived cytokines could be envisaged in the non-responders.

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“…9,10 Indeed, in several clinical settings, plasma LBP seems to reflect better the long-term exposure to bacteria and their endotoxins than endotoxin itself. 9,11,12 However, no study has yet investigated plasma LBP levels in cirrhosis. The goals of this study were to investigate (1) whether plasma LBP levels are increased in cirrhosis, and (2) if so, whether cirrhotic patients with high LBP levels exhibit more pronounced immune disturbance and hyperdynamic circulatory state.…”

mentioning

confidence: 99%

Increased lipopolysaccharide binding protein in cirrhotic patients with marked immune and hemodynamic derangement

et al. 2003

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Intestinal bacterial overgrowth and translocation, both common in cirrhosis with ascites, may lead to the activation of monocytes and lymphocytes, increased levels of proinflammatory cytokines, and enhanced synthesis of nitric oxide present in cirrhosis. Bacterial endotoxin promotes the synthesis of lipopolysaccharide (LPS)-binding protein (LBP), and forms a LPS-LBP complex that binds to CD14. This study was designed to evaluate LBP levels and their correlation to the immune response and the hemodynamic status in cirrhotic patients. Plasma LBP, endotoxin, soluble CD14 (sCD14), cytokines, renin, nitrites, and systemic vascular resistance were determined before and 4 weeks after norfloxacin or placebo in 102 cirrhotic patients and 30 controls. LBP was elevated in 42% of ascitic cirrhotic patients (15.7 ؎ 0.7 versus 6.06 ؎ 0.5 g/mL, P < .01). In 60% of high LBP patients, endotoxin was within normal range. Among ascitic patients, those with high LBP showed greater (P < .05) levels of sCD14, tumor necrosis factor ␣ (TNF-␣), interleukin 6 (IL-6), nitrites ؉ nitrates (NOx)/creatinine, and renin, and lower vascular resistance. In the cirrhotic patients with high LBP, norfloxacin normalized (P < .01) LBP (from 16.6 ؎ 0.5 to 5.82 ؎ 0.8 g/mL) and sCD14; reduced the level of cytokines, NOx/creatinine, and renin; and increased vascular resistance; but lacked effect in patients with normal LBP. Portal pressure was unchanged after norfloxacin in another group of 18 cirrhotic patients with high and 19 with normal LBP. In conclusion, the subset of ascitic cirrhotic patients with marked immune and hemodynamic derangement is identified by increased LBP levels. Amelioration of these abnormalities by norfloxacin suggests the involvement of enteric bacteria or their products in the triggering of the process. (HEPATOLOGY 2003;37:208-217.)

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Relationship between Plasma Levels of Lipopolysaccharide (LPS) and LPS‐Binding Protein in Patients with Severe Sepsis and Septic Shock

Cited by 537 publications

References 37 publications

Effects of bone marrow mesenchymal stem cells on the cardiac function and immune system of mice with endotoxemia

Effects of bone marrow mesenchymal stem cells on the cardiac function and immune system of mice with endotoxemia

Review: The role of the liver in the response to LPS: experimental and clinical findings

Increased lipopolysaccharide binding protein in cirrhotic patients with marked immune and hemodynamic derangement

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