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Neurocritical Care
Published in: Neurocritical Care 1/2015

01-08-2015 | Translational Research

Hypothermia Reduces but Hyperthermia Augments T Cell-Derived Release of Interleukin-17 and Granzyme B that Mediate Neuronal Cell Death

Authors: Tomohiro Matsui, Natsumi Kawahara, Arisa Kimoto, Yusuke Yoshida

Published in: Neurocritical Care | Issue 1/2015

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Abstract

Background

T cells infiltrate into the infarcted brain within days after cerebral ischemia and play essential roles in exacerbating the delayed phase of the brain injury by producing pro-inflammatory factors. However, the involvement of these factors in brain damage is also demonstrated systemically. Such periphery–brain abnormalities are interesting because they may constitute a pathway to the central nervous system (CNS), which may be a target of therapeutic hypothermia. Although this therapy protects neurons after severe brain damage, the underlying mechanisms are partly understood. We examined the effects of hypothermic and hyperthermic cultures on peripheral T cell-derived release of interleukin (IL)-17 and granzyme B (GrB) and evaluated whether and how these factors induced neurotoxicity and activated brain endothelial cells.

Methods

We determined levels of IL-17 and GrB produced by several activated, IL-1β/IL-23-treated activated T cells (naïve CD4+, CD4+, CD8+, and γδ T cells obtained from healthy humans) under hypothermia, normothermia, and hyperthermia. The viability of neuronal SH-SY5Y cells treated with IL-17 or GrB and mRNA expression of adhesion molecules/chemokines by brain endothelial bEND.3 cells treated with IL-17 were also measured.

Results

Compared with normothermia, IL-17 and GrB release in these T cells was reduced by hypothermia but augmented by hyperthermia. IL-17 and GrB caused the death of neuronal SH-SY5Y cells, and IL-17 upregulated mRNA expression of several adhesion molecules/chemokines in bEND.3 cells; both effects were concentration-dependent.

Conclusion

Hypothermia reduced but hyperthermia augmented T cell-derived release of IL-17 and GrB that mediate neuronal cell death, suggesting that the attenuation of T cell-derived release of these factors by therapeutic hypothermia leads to the inhibition of neuronal cell death in the delayed phase of brain injury. Moreover, hypothermia may suppress but hyperthermia may promote the recruitment of inflammatory cells to CNS by regulating brain endothelial activation of IL-17.
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Metadata
Title
Hypothermia Reduces but Hyperthermia Augments T Cell-Derived Release of Interleukin-17 and Granzyme B that Mediate Neuronal Cell Death
Authors
Tomohiro Matsui
Natsumi Kawahara
Arisa Kimoto
Yusuke Yoshida
Publication date
01-08-2015
Publisher
Springer US
Published in
Neurocritical Care / Issue 1/2015
Print ISSN: 1541-6933
Electronic ISSN: 1556-0961
DOI
https://doi.org/10.1007/s12028-014-0094-5

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