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Cryobiology. 2008 Dec;57(3):216-22. doi: 10.1016/j.cryobiol.2008.08.005. Epub 2008 Aug 29.

Hypothermia downregulates inflammation but enhances IL-6 secretion by stimulated endothelial cells.

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  • 1Department of Pediatric Cradiology, Charité Universitaetsmedizin Berlin, Berlin, Germany.

Abstract

Hypothermia is a standard method for organ protection during cardiac surgery in children. However, the mechanisms of hypothermia-induced cell protection have not yet been clearly established. Therefore, the aim of our studies was to elucidate molecular effects of clinically relevant mild and deep hypothermia on endothelial cells. The endothelium plays a pivotal role in the interaction between blood cells and actively participates in complex inflammatory events. We isolated primary human umbilical vein endothelial cells (HUVEC) and investigated cell viability, proliferation and inflammatory characteristics after TNF-alpha stimulation under mild (32 degrees C) and deep (17 degrees C) hypothermia in comparison to normothermia (37 degrees C). As a protective mechanism of endothelial cells kept under hypothermic conditions we found a significant upregulation of the antiapoptotic protein Bcl-2, resulting in the same cell viability under hypothermic conditions. Unexpectedly we demonstrated significantly higher IL-6 release after 6h of mild hypothermia. In contrast, hypothermia diminished inflammatory chemokines such as IL-8, MCP-1 and COX-2 protein expression which could lead to reduced leukocyte recruitment under hypothermia. Underlying mechanisms of this downregulation were found to be reduced ERK 1/2 phosphorylation and incomplete IkappaB-alpha degradation resulting in reduced NFkappaB-dependent proinflammatory gene expression. The upregulation of Bcl-2 protein and the higher IL-6 release after 6h of mild hypothermia are new and interesting cellular mechanisms of hypothermia in endothelial cell biology. Both factors may play a major role as cell protective mechanisms in hypothermia.

PMID:
18790695
[PubMed - indexed for MEDLINE]
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