Endotoxin-induced microparticle formation is subject to tolerance development in humans

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Endotoxin-induced microparticle formation is subject to tolerance development in humans

Methods Formation of MP was studied in 8 healthy male subjects exposed to intravenous E. coli endotoxin (LPS; 2 ng/kg body weight) who were re-challenged after 17 ± 11 days. In addition, intravenous vitamin C (25 g) or placebo was administered 3.5 hours after LPS on alternate trial days in random order. Venous blood samples were taken before, 3 h and 6 h after LPS administration. MP were detect...

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SMAD4 is required for development of maximal endotoxin tolerance.

Initial exposure of monocytes/macrophages to LPS induces hyporesponsiveness to a second challenge with LPS, a phenomenon termed LPS tolerance. Molecular mechanisms responsible for endotoxin tolerance are not well defined. We and others have shown that IL-1R-associated kinase (IRAK)-M and SHIP-1 proteins, negative regulators of TLR4 signaling, increase in tolerized cells. TGF-beta1, an anti-infl...

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Potential New Markers of Inflammation-Induced Renal Injury Subside when Endotoxin Tolerance Develops in Humans

Renal injury is a common clinical problem in the critically ill patient, and is associated with poor outcome [1,2]. Two large multicentre cohort studies reported previously the occurrence of renal injury in an estimated 30-40% of all patients admitted to the ICU [3,4]. Furthermore, critically ill patients who develop renal injury and require renal replacement therapy, have mortality rates of 50...

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Blockade of nitric oxide formation in the rat brain does not disturb development of endotoxin tolerance.

The involvement of nitric oxide (NO) in tolerance development to endotoxin has been proposed because peripherally administered NG-nitro-L-arginine methyl ester (L-NAME) (NO synthases inhibitor) delays the endotoxin tolerance formation. Since L-NAME is capable of crossing the blood-brain barrier, the question arises of where activity of NO synthases (inside or outside the blood-brain barrier) is...

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Compartmentalization of tolerance to endotoxin.

BACKGROUND Tolerance to endotoxin has been defined and analyzed either entirely in vivo or entirely in vitro. In contrast, the hyporeactivity of circulating leukocytes reported in patients with sepsis, and often referred to as the phenomenon of tolerance to endotoxin, is an ex vivo observation. Therefore, our objective was to set up an ex vivo model of tolerance to endotoxin. METHODS Mice wer...

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ژورنال

عنوان ژورنال: BMC Pharmacology

سال: 2010

ISSN: 1471-2210

DOI: 10.1186/1471-2210-10-s1-a37