Endotoxin tolerance variation over 24 h during porcine endotoxemia: association with changes in circulation and organ dysfunction.

Endotoxin tolerance (ET), defined as reduced inflammatory responsiveness to endotoxin challenge following a first encounter with endotoxin, is an extensively studied phenomenon. Although reduced mortality and morbidity in the presence of ET has been demonstrated in animal studies, little is known ab...

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Autores principales: Markus Castegren, Paul Skorup, Miklós Lipcsey, Anders Larsson, Jan Sjölin
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Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/5927cbb8a1624119b0c919a942173764
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spelling oai:doaj.org-article:5927cbb8a1624119b0c919a9421737642021-11-18T08:02:03ZEndotoxin tolerance variation over 24 h during porcine endotoxemia: association with changes in circulation and organ dysfunction.1932-620310.1371/journal.pone.0053221https://doaj.org/article/5927cbb8a1624119b0c919a9421737642013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23326400/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Endotoxin tolerance (ET), defined as reduced inflammatory responsiveness to endotoxin challenge following a first encounter with endotoxin, is an extensively studied phenomenon. Although reduced mortality and morbidity in the presence of ET has been demonstrated in animal studies, little is known about the temporal development of ET. Further, in acute respiratory distress syndrome ET correlates to the severity of the disease, suggesting a complicated relation between ET and organ dysfunction. Eighteen pigs were subjected to intensive care and a continuous endotoxin infusion for 24 h with the aim to study the time course of early ET and to relate ET to outcome in organ dysfunction. Three animals served as non-endotoxemic controls. Blood samples for cytokine analyses were taken and physiological variables registered every third hour. Production of TNF-α, IL-6, and IL-10 before and after endotoxin stimulation ex vivo was measured. The difference between cytokine values after and before ex vivo LPS stimulation (Δ-values) was calculated for all time points. ΔTNF-α was employed as the principal marker of ET and lower ΔTNF-α values were interpreted as higher levels of ET. During endotoxin infusion, there was suppression of ex vivo productions of TNF-α and IL-6 but not of IL-10 in comparison with that at 0 h. The ex vivo TNF-α values followed another time concentration curve than those in vivo. ΔTNF-α was at the lowest already at 6 h, followed by an increase during the ensuing hours. ΔTNF-α at 6 h correlated positively to blood pressure and systemic vascular resistance and negatively to cardiac index at 24 h. In this study a temporal variation of ET was demonstrated that did not follow changes in plasma TNF-α concentrations. Maximal ET occurred early in the course and the higher the ET, the more hyperdynamic the circulation 18 h later.Markus CastegrenPaul SkorupMiklós LipcseyAnders LarssonJan SjölinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e53221 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Markus Castegren
Paul Skorup
Miklós Lipcsey
Anders Larsson
Jan Sjölin
Endotoxin tolerance variation over 24 h during porcine endotoxemia: association with changes in circulation and organ dysfunction.
description Endotoxin tolerance (ET), defined as reduced inflammatory responsiveness to endotoxin challenge following a first encounter with endotoxin, is an extensively studied phenomenon. Although reduced mortality and morbidity in the presence of ET has been demonstrated in animal studies, little is known about the temporal development of ET. Further, in acute respiratory distress syndrome ET correlates to the severity of the disease, suggesting a complicated relation between ET and organ dysfunction. Eighteen pigs were subjected to intensive care and a continuous endotoxin infusion for 24 h with the aim to study the time course of early ET and to relate ET to outcome in organ dysfunction. Three animals served as non-endotoxemic controls. Blood samples for cytokine analyses were taken and physiological variables registered every third hour. Production of TNF-α, IL-6, and IL-10 before and after endotoxin stimulation ex vivo was measured. The difference between cytokine values after and before ex vivo LPS stimulation (Δ-values) was calculated for all time points. ΔTNF-α was employed as the principal marker of ET and lower ΔTNF-α values were interpreted as higher levels of ET. During endotoxin infusion, there was suppression of ex vivo productions of TNF-α and IL-6 but not of IL-10 in comparison with that at 0 h. The ex vivo TNF-α values followed another time concentration curve than those in vivo. ΔTNF-α was at the lowest already at 6 h, followed by an increase during the ensuing hours. ΔTNF-α at 6 h correlated positively to blood pressure and systemic vascular resistance and negatively to cardiac index at 24 h. In this study a temporal variation of ET was demonstrated that did not follow changes in plasma TNF-α concentrations. Maximal ET occurred early in the course and the higher the ET, the more hyperdynamic the circulation 18 h later.
format article
author Markus Castegren
Paul Skorup
Miklós Lipcsey
Anders Larsson
Jan Sjölin
author_facet Markus Castegren
Paul Skorup
Miklós Lipcsey
Anders Larsson
Jan Sjölin
author_sort Markus Castegren
title Endotoxin tolerance variation over 24 h during porcine endotoxemia: association with changes in circulation and organ dysfunction.
title_short Endotoxin tolerance variation over 24 h during porcine endotoxemia: association with changes in circulation and organ dysfunction.
title_full Endotoxin tolerance variation over 24 h during porcine endotoxemia: association with changes in circulation and organ dysfunction.
title_fullStr Endotoxin tolerance variation over 24 h during porcine endotoxemia: association with changes in circulation and organ dysfunction.
title_full_unstemmed Endotoxin tolerance variation over 24 h during porcine endotoxemia: association with changes in circulation and organ dysfunction.
title_sort endotoxin tolerance variation over 24 h during porcine endotoxemia: association with changes in circulation and organ dysfunction.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/5927cbb8a1624119b0c919a942173764
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AT mikloslipcsey endotoxintolerancevariationover24hduringporcineendotoxemiaassociationwithchangesincirculationandorgandysfunction
AT anderslarsson endotoxintolerancevariationover24hduringporcineendotoxemiaassociationwithchangesincirculationandorgandysfunction
AT jansjolin endotoxintolerancevariationover24hduringporcineendotoxemiaassociationwithchangesincirculationandorgandysfunction
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