Endotoxaemia: a review with implications for the horse

Werners, Arno; Bull, Sarah; Fink‐Gremmels, Johanna

doi:10.2746/0425164054529418

Cited by 95 publications

(81 citation statements)

References 217 publications

(228 reference statements)

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“…After binding of LPS to LBP and CD14, LPS is recognized by MD2 which binds the lipid A part of LPS (Werners et al 2005). MD2 then associates with the extracellular domain of TLR4 thereby activating intracellular phosphorylation cascades including the MAPK and NF-кB activation pathways leading to the production of pro-inflammatory cytokines (Werners et al 2005).…”

Section: Myeloid Differentiation Protein 2 (Md2) Lps Signaling Throumentioning

confidence: 99%

“…CD14 is present in a soluble form (sCD14) in blood or as a glycosylphosphatidylinositol (GPI)-linked form (mCD14) on the cell surface of monocytes, macrophages and neutrophils (Werners et al 2005). Binding of LPS to soluble CD14 (sCD14)…”

Section: High-density Lipoproteins (Hdl)mentioning

confidence: 99%

“…are processed through the trans-Golgi-apparatus secretory pathway and reside on the cell surface as a mature protein complex (Latz et al 2002;Werners et al 2005). After binding of LPS to LBP and CD14, LPS is recognized by MD2 which binds the lipid A part of LPS (Werners et al 2005).…”

Section: Myeloid Differentiation Protein 2 (Md2) Lps Signaling Throumentioning

confidence: 99%

“…This is mediated by a complex series of biochemical processes, initiated by cellular binding, transmembrane signaling, activation of cytokine expression leading to systemic inflammation and circulatory shock. Once LPS-LBP complexes are bound to Cluster of Differentiation antigen 14 (CD14) on the surface of phagocytes, CD14 interacts with Toll-like receptor 4 (TLR-4) resulting in activation of nuclear factor кB (NF-кB) and mitogen-activated protein kinase (MAPK) signaling pathways and subsequent production of pro-inflammatory (TNF-α, IL-1, IL-6, IL-8, IL-12) and anti-inflammatory (IL-10, TGF-β) cytokines (Schutt 1999;Werners et al 2005). TNF-α represents the most important and most potent pro-inflammatory mediator involved in endotoxic shock.…”

Section: Chapter 1 Endotoxemia In Horses Endotoxinmentioning

confidence: 99%

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Induction and characterization of endotoxin tolerance in equine peripheral blood mononuclear cells in vitro

Frellstedt

McKenzie

Barrett

et al. 2012

Veterinary Immunology and Immunopathology

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Endotoxemia is responsible for severe illness in horses. Individuals can become unresponsive to the endotoxin molecule after an initial exposure; this phenomenon has been called developing a state of 'endotoxin tolerance' (ET). ET has been induced in horses in vivo; however, cytokine expression associated with ET has not been investigated. The purpose of this study was to develop and validate a method for inducing ET in equine peripheral blood mononuclear cells (PBMCs) in vitro, and to describe the cytokine profile which is associated with the ET.Blood was collected from 6 healthy horses and PBMCs were isolated. ET was induced by culturing cells with three concentrations of endotoxin given to induce ET, and evaluated after a second dose of endotoxin given to challenge the cells. The relative mRNA expression of IL-10 and IL-12 was measured by use of quantitative PCR.ET was induced in all cells (n=6) exposed to the 2-step endotoxin challenge. In PBMCs treated with 1.0 ng/ml of endotoxin followed by challenge with 10 ng/ml of endotoxin, the relative mRNA expression of IL-10 in tolerized cells was not different from positive control cells. In contrast, the relative mRNA expression of IL-12 in tolerized cells was decreased by 15-fold after the second endotoxin challenge compared with positive control cells.This experiment demonstrated a reliable method for the ex vivo induction of ET in equine PBMCs. A marked suppression of IL-12 production is associated with ET. The production of IL-10 was not altered in ET in our model.

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Section: Myeloid Differentiation Protein 2 (Md2) Lps Signaling Throumentioning

confidence: 99%

Section: High-density Lipoproteins (Hdl)mentioning

confidence: 99%

Section: Myeloid Differentiation Protein 2 (Md2) Lps Signaling Throumentioning

confidence: 99%

Section: Chapter 1 Endotoxemia In Horses Endotoxinmentioning

confidence: 99%

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Induction and characterization of endotoxin tolerance in equine peripheral blood mononuclear cells in vitro

Frellstedt

McKenzie

Barrett

et al. 2012

Veterinary Immunology and Immunopathology

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“…[2][3][4] Incorporated in the outer membrane of gram-negative bacteria is LPS (endotoxin), which plays a pivotal role in host response to bacterial invasion by promoting inflammation via production of prostaglandins, serotonin, kinins, inflammatory interleukins, and other mediators. 5,6 Clinically, endotoxemia has been reported in 10% to 50% of neonatal foals (≤ 14 days of age) evaluated at equine referral hospitals for treatment of presumed septicemia. 7,8 Objective-To evaluate the effect of IV administration of polymyxin B on clinical and serum biochemical variables in foals with experimental endotoxemia.…”

mentioning

confidence: 99%

Effects of intravenous administration of polymyxin B in neonatal foals with experimental endotoxemia

Wong¹,

Sponseller²,

Alcott³

et al. 2013

javma

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Objective—To evaluate the effect of IV administration of polymyxin B on clinical and serum biochemical variables in foals with experimental endotoxemia. Design—Prospective experimental study. Animals—14 healthy neonatal foals. Procedures—Foals were randomly assigned to a treatment or control group and were administered a single dose of lipopolysaccharide (0.5 μg/kg [0.23 μg/lb]) IV over 30 minutes. The treatment group received polymyxin B (6,000 U/kg [2,727 U/lb], IV) immediately after completion of lipopolysaccharide infusion; the control group was administered an equal volume of saline (0.9% NaCl) solution. Subsequent doses of polymyxin B or saline solution were administered IV at 8 and 16 hours. Blood was collected at various time points, and outcome variables, including heart rate, respiratory rate, rectal temperature, attitude score, WBC count, neutrophil count, lymphocyte count, monocyte count, platelet count, Hct, blood lactate concentration, blood glucose concentration, serum tumor necrosis factor-α concentration, and plasma thromboxane B2 concentration, were measured. Urine was collected prior to and after experimentation to determine whether nephrotoxicosis was associated with treatment. Results—The treatment group had significantly lower blood lactate concentration and serum tumor necrosis factor-α and plasma thromboxane B2 concentrations and had higher blood glucose concentrations and better attitude scores, compared with the control group, at various time points during the study. No other significant differences and no evidence of overt nephrotoxicosis were detected. Conclusions and Clinical Relevance—Administration of polymyxin B IV in healthy neonatal foals challenged with lipopolysaccharide attenuated some clinical and serum biochemical derangements associated with endotoxemia.

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Postoperative Complications

Hassel¹

2012

Practical Guide to Equine Colic

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Endotoxaemia: a review with implications for the horse

Cited by 95 publications

References 217 publications

Induction and characterization of endotoxin tolerance in equine peripheral blood mononuclear cells in vitro

Induction and characterization of endotoxin tolerance in equine peripheral blood mononuclear cells in vitro

Effects of intravenous administration of polymyxin B in neonatal foals with experimental endotoxemia

Postoperative Complications

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