Endotoxin tolerance does not limit mild ischemia-reperfusion injury in humans in vivo

Draisma, Annelies; Goeij, Moniek de; Wouters, Carine; Riksen, Niels P.; Oyen, Wim J.G.; Rongen, Gerard A.; Boerman, Otto C.; Deuren, Marcel van; Hoeven, Johannes G. van der; Pickkers, Peter

doi:10.1177/1753425909105548

Cited by 8 publications

(12 citation statements)

References 43 publications

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“…Although very low circulating cytokine levels were found, a small, but significant attenuation of TNF-␣, IL-6, and IL-1RA plasma levels was observed upon the second LPS administration (18). Earlier work from our group has shown that after LPS administration for 5 consecutive days in healthy volunteers, the cytokine response is virtually nullified at day 5 (11,19), and similar results were observed in LPStreated cancer patients (20).…”

Section: Discussionsupporting

confidence: 86%

Differential ex vivo and in vivo endotoxin tolerance kinetics following human endotoxemia*

Kox

Kleijn

Pompe

et al. 2011

Critical Care Medicine

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While ex vivo lipopolysaccharide tolerance quickly resolves, in vivo lipopolysaccharide tolerance persists for at least 2 wks. These findings strengthen the notion that the in vivo response to lipopolysaccharide is mediated by tissue-resident macrophages and that ex vivo stimulation does not accurately reflect the in vivo innate immune response. Intervention studies utilizing the human endotoxemia model should be performed using parallel groups rather than a crossover design.

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Section: Discussionsupporting

confidence: 86%

Differential ex vivo and in vivo endotoxin tolerance kinetics following human endotoxemia*

Kox

Kleijn

Pompe

et al. 2011

Critical Care Medicine

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“…Published i n vivo studies show a general decrease in inflammatory cytokine production from macrophages after repeated LPS dosing, a phenomenon known as LPS or endotoxin tolerance [39, 40]. This effect is considered a natural cellular response to prevent uncontrolled inflammation [41–43], and is readily apparent in cultured primary-derived macrophages in this and other studies [44].…”

Section: Discussionmentioning

confidence: 73%

Cell–cell signaling in co-cultures of macrophages and fibroblasts

Holt¹,

Chamberlain²,

Grainger³

2010

Biomaterials

116

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The foreign body response (FBR) comprises a general, ubiquitous host tissue-based reaction to implanted materials. In vitro cell-based models are frequently employed to study FBR mechanisms involving cell signaling responses to materials. However, these models often study only one cell type, identify only limited signals, and cannot accurately represent the complexity of in vivo inflammatory signaling. To address this issue, a cell co-culture system involving two primary effector cells of the FBR, macrophages and fibroblasts, was employed. Cell-cell signaling systems were monitored between these cell types, including long-term 1) culture of one cell type in conditioned media from the other cell type, 2) non-contacting cell co-cultures (paracrine signaling), and 3) contact co-cultures (juxtacrine signaling) of primary-and secondary-derived cells. Cell culture media and cell images were collected on Days 1, 2, 3, 7, 14, and 21 and changes in soluble protein secretion, cellular behavior, and morphology were assessed. Primary-and secondary-derived cells responded uniquely during each signaling scenario and to one another. In general higher in vitro fidelity to FBRlike responses was found in primary cell co-cultures compared to their mono-cultures and all secondary cell cultures.

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“…102 In the same model, endothelial dysfunction gradually declines as endotoxin tolerance emerges, 136 whereas LPS tolerance does not seem to protect against ischemia-reperfusion injury. 137 The repeated-exposure model has also been used for the study of sepsis-induced immunoparalysis, where IFN-γ treatment has partially reversed immune suppression and furthered pharmacologic interest for immunostimulation in sepsis. 138 Though these findings provide key initial insights into the elements of endotoxin tolerance, much research is still needed to elucidate the role of repeated LPS exposure on cardiometabolic physiology.…”

Section: Limitations and Challenges Of The Modelmentioning

confidence: 99%

Human Experimental Endotoxemia in Modeling the Pathophysiology, Genomics, and Therapeutics of Innate Immunity in Complex Cardiometabolic Diseases

Patel

Shah

Reilly³

2015

ATVB

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Inflammation is a fundamental feature of several complex cardiometabolic diseases. Indeed, obesity, insulin resistance, metabolic dyslipidemia, and atherosclerosis are all closely linked inflammatory states. Increasing evidence suggests that the infectious, biome-related or endogenous activation of the innate immune system may contribute to the development of metabolic syndrome and cardiovascular disease. Here we describe the human experimental endotoxemia model for the specific study of innate immunity in understanding further the pathogenesis of cardiometabolic disease. In a controlled, experimental setting, administration of an intravenous bolus of purified Escherichia coli endotoxin activates innate immunity in healthy human volunteers. During endotoxemia, changes emerge in glucose metabolism, lipoprotein composition, and lipoprotein functions that closely resemble those observed chronically in inflammatory cardiovascular disease risk states. In this review we describe the transient systemic inflammation and specific metabolic consequences that develop during human endotoxemia. Such a model provides a controlled induction of systemic inflammation, eliminates confounding, undermines reverse causation, and possesses unique potential as a starting point for genomic screening and testing of novel therapeutics for treatment of the inflammatory underpinning of cardiometabolic disease.

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Endotoxin tolerance does not limit mild ischemia-reperfusion injury in humans in vivo

Cited by 8 publications

References 43 publications

Differential ex vivo and in vivo endotoxin tolerance kinetics following human endotoxemia*

Differential ex vivo and in vivo endotoxin tolerance kinetics following human endotoxemia*

Cell–cell signaling in co-cultures of macrophages and fibroblasts

Human Experimental Endotoxemia in Modeling the Pathophysiology, Genomics, and Therapeutics of Innate Immunity in Complex Cardiometabolic Diseases

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