Impact of molecular mimicry on the clinical course and outcome of sepsis syndrome

Kristóf, Katalin; Madách, Krisztina; Sándor, Noémi; Iványi, Zsolt; Király, András; Erdei, Anna; Tulassay, Eszter; Gál, János; Bajtay, Zsuzsa

doi:10.1016/j.molimm.2011.09.023

Cited by 8 publications

(9 citation statements)

References 26 publications

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“…Previous investigators have found increased incidence of sepsis and severe sepsis in the underweight population [43] as well as higher disease severity at admission [44]. The trend towards worsened survival in this cohort does not appear to be due to increased incidence of comorbid conditions including cancer, renal disease, or liver disease as these conditions were not present at higher rates in patients who were underweight.…”

Section: Discussionmentioning

confidence: 46%

The impact of obesity on sepsis mortality: a retrospective review

et al. 2013

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BackgroundRecent sepsis guidelines have focused on the early identification and risk stratification of patients on presentation. Obesity is associated with alterations in multiple inflammatory regulators similar to changes seen in sepsis, suggesting a potential interaction between the presence of obesity and the severity of illness in sepsis.MethodsWe performed a retrospective chart review of patients admitted with a primary billing diagnosis of sepsis at a single United States university hospital from 2007 to 2010. Seven hundred and ninety-two charts were identified meeting inclusion criteria. Obesity was defined as a body mass index (BMI) ≥ 30 kg/m2. The data recorded included age, race, sex, vital signs, laboratory values, length of stay, comorbidities, weight, height, and survival to discharge. A modified APACHE II score was calculated to estimate disease severity. The primary outcome variable was inpatient mortality.ResultsSurvivors had higher average BMI than nonsurvivors (27.6 vs. 26.3 kg/m2, p = 0.03) in unadjusted analysis. Severity of illness and comorbid conditions including cancer were similar across BMI categories. Increased incidence of diabetes mellitus type 2 was associated with increasing BMI (p < 0.01) and was associated with decreased mortality, with an odds ratio of 0.53 compared with nondiabetic patients. After adjusting for age, gender, race, severity of illness, length of stay, and comorbid conditions, the trend of decreased mortality for increased BMI was no longer statistically significant, however diabetes continued to be strongly protective (odds ratio 0.52, p = 0.03).ConclusionsThis retrospective analysis suggests obesity may be protective against mortality in septic inpatients. The protective effect of obesity may be dependent on diabetes, possibly through an unidentified hormonal intermediary. Further prospective studies are necessary to elaborate the specific mechanism of this protective effect.

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Section: Discussionmentioning

confidence: 46%

The impact of obesity on sepsis mortality: a retrospective review

et al. 2013

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“…The components that make up EBF include the synthesis and release of mucus from goblet cells, transcytosis of dimeric secretory IgA [which is also lost with TPN (Fukatsu and Kudsk, 2011)], intraluminal movement of water, and the physical integrity of the epithelium itself (Clayburgh et al, 2004). Breakdown of this barrier can lead to the translocation of intestinal microbiota and/or endotoxin, which are thought to contribute to TPN-related sepsis (Kristof et al, 2011). …”

Section: Physiologic and Immunologic Changes With Tpn In A Mouse Modelmentioning

confidence: 99%

Intestinal epithelial cell apoptosis and loss of barrier function in the setting of altered microbiota with enteral nutrient deprivation

Demehri

Barrett

Ralls

et al. 2013

Front. Cell. Infect. Microbiol.

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Total parenteral nutrition (TPN), a commonly used treatment for patients who cannot receive enteral nutrition, is associated with significant septic complications due in part to a loss of epithelial barrier function (EBF). While the underlying mechanisms of TPN-related epithelial changes are poorly understood, a mouse model of TPN-dependence has helped identify several contributing factors. Enteral deprivation leads to a shift in intestinal microbiota to predominantly Gram-negative Proteobacteria. This is associated with an increase in expression of proinflammatory cytokines within the mucosa, including interferon-γ and tumor necrosis factor-α. A concomitant loss of epithelial growth factors leads to a decrease in epithelial cell proliferation and increased apoptosis. The resulting loss of epithelial tight junction proteins contributes to EBF dysfunction. These mechanisms identify potential strategies of protecting against TPN-related complications, such as modification of luminal bacteria, blockade of proinflammatory cytokines, or growth factor replacement.

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“…3) The resulting disruption of the barrier function leads to increased intestinal permeability and bacterial translocation [21,22]. The intestinal barrier that prevents the permeation of LPS via paracellular route consists of tight junctions and adherens junctions, including occludin, claudin, tricellulin, ZO-1 and E-cadherin [23].…”

Section: Discussionmentioning

confidence: 99%

Soybean Oil-Based Lipid Emulsion Increases Intestinal Permeability of Lipopolysaccharide in Caco-2 Cells by Downregulation of P-Glycoprotein via ERK-FOXO 3a Pathway

Yan

Zhu

et al. 2016

Cell Physiol Biochem

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Background and Aims: Elevated intestinal permeability of lipopolysaccharide (LPS) is a major complication for patients with parenteral nutrition (PN), but the pathogenesis is poorly understood. Intestinal P-glycoprotein (P-gp) is one of the efflux transporters that contribute to restricting the permeability of lipopolysaccharide via transcellular route. P-gp expression may be regulated by PN ingredients, and thus this study sought to investigate the effect of PN on the expression of P-gp and to elucidate the underlying mechanism in vitro. Methods: Caco-2 cells were treated with PN ingredients. Changes in P-gp expression and function were determined and the role of ERK-FOXO 3a pathway was studied. Transport studies of FITC-lipopolysaccharide (FITC-LPS) across Caco-2 cell monolayers were also performed. Results: Among PN ingredients, soybean oil-based lipid emulsion (SOLE) exhibited significant inhibitory effect on P-gp expression and function. This regulation was mediated via activation of ERK pathway with subsequent nuclear exclusion of FOXO 3a. Importantly, P-gp participated in antagonizing the permeation of FITC-LPS (apical to basolateral) across Caco-2 cell monolayers. SOLE significantly increased the permeability of FITC-LPS (apical to basolateral), which was associated with impaired P-gp function. Conclusions: The expression and function of intestinal P-gp is suppressed by SOLE in vitro.

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Impact of molecular mimicry on the clinical course and outcome of sepsis syndrome

Cited by 8 publications

References 26 publications

The impact of obesity on sepsis mortality: a retrospective review

The impact of obesity on sepsis mortality: a retrospective review

Intestinal epithelial cell apoptosis and loss of barrier function in the setting of altered microbiota with enteral nutrient deprivation

Soybean Oil-Based Lipid Emulsion Increases Intestinal Permeability of Lipopolysaccharide in Caco-2 Cells by Downregulation of P-Glycoprotein via ERK-FOXO 3a Pathway

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