An in vitro model to consider the effect of 2 mM glutamine and KNK437 on endotoxin-stimulated release of heat shock protein 70 and inflammatory mediators
File(s)
Accepted version
Author(s)
Marino, LV
Pathan, N
Meyer, RW
Wright, VJ
Habibi, P
Type
Journal Article
Abstract
Objective
Glutamine has been shown to promote the release of heat shock protein 70 (HSP70) both within experimental in vitro models of sepsis and in adults with septic shock. This study aimed to investigate the effects of 2 mM glutamine and an inhibitor of HSP70 (KNK437) on the release of HSP70 and inflammatory mediators in healthy adult volunteers.
Methods
An in vitro whole blood endotoxin stimulation assay was used.
Results
The addition of 2 mM glutamine significantly increased HSP70 levels over time (P < 0.05). HSP70 release had a positive correlation at 4 h with IL-1 β (r = 0.51, P = 0.03) and an inverse correlation with TNF-α (r = −0.56, P = 0.02) and IL-8 levels (r = −0.52, P = 0.03), and there were no significant correlations between HSP70 and IL6 or IL-10 or glutamine. Glutamine supplementation significantly (P < 0.05) attenuated the release of IL-10 at 4 h and IL-8 at 24 h, compared with conditions without glutamine. In endotoxin-stimulated blood there were no significant differences in the release of IL-6, TNF-α, and IL-1 β with glutamine supplementation at 4 and 24 h. However, glutamine supplementation (2 mM) appeared to attenuate the release of inflammatory mediators (IL-1 β, IL-6, TNF-α), although this effect was not statistically significant. The addition of KNK437, a HSP70 inhibitor, significantly diminished HSP70 release, which resulted in lower levels of inflammatory mediators (P < 0.05).
Conclusion
Glutamine supplementation promotes HSP70 release in an experimental model of sepsis. After the addition of KNK437, the effects of glutamine on HSP70 and inflammatory mediator release appear to be lost, suggesting that HSP70 in part orchestrates the inflammatory mediator response to sepsis. The clinical implications require further investigation.
Glutamine has been shown to promote the release of heat shock protein 70 (HSP70) both within experimental in vitro models of sepsis and in adults with septic shock. This study aimed to investigate the effects of 2 mM glutamine and an inhibitor of HSP70 (KNK437) on the release of HSP70 and inflammatory mediators in healthy adult volunteers.
Methods
An in vitro whole blood endotoxin stimulation assay was used.
Results
The addition of 2 mM glutamine significantly increased HSP70 levels over time (P < 0.05). HSP70 release had a positive correlation at 4 h with IL-1 β (r = 0.51, P = 0.03) and an inverse correlation with TNF-α (r = −0.56, P = 0.02) and IL-8 levels (r = −0.52, P = 0.03), and there were no significant correlations between HSP70 and IL6 or IL-10 or glutamine. Glutamine supplementation significantly (P < 0.05) attenuated the release of IL-10 at 4 h and IL-8 at 24 h, compared with conditions without glutamine. In endotoxin-stimulated blood there were no significant differences in the release of IL-6, TNF-α, and IL-1 β with glutamine supplementation at 4 and 24 h. However, glutamine supplementation (2 mM) appeared to attenuate the release of inflammatory mediators (IL-1 β, IL-6, TNF-α), although this effect was not statistically significant. The addition of KNK437, a HSP70 inhibitor, significantly diminished HSP70 release, which resulted in lower levels of inflammatory mediators (P < 0.05).
Conclusion
Glutamine supplementation promotes HSP70 release in an experimental model of sepsis. After the addition of KNK437, the effects of glutamine on HSP70 and inflammatory mediator release appear to be lost, suggesting that HSP70 in part orchestrates the inflammatory mediator response to sepsis. The clinical implications require further investigation.
Date Issued
2015-09-30
Date Acceptance
2015-09-13
Citation
Nutrition, 2015, 32 (3), pp.375-383
ISSN
0899-9007
Publisher
Elsevier
Start Page
375
End Page
383
Journal / Book Title
Nutrition
Volume
32
Issue
3
Copyright Statement
© 2015 Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Subjects
Science & Technology
Life Sciences & Biomedicine
Nutrition & Dietetics
KNK437
Glutamine
HSP70
Sepsis
Inflammatory mediators
HEAT-SHOCK-PROTEIN
NF-KAPPA-B
RESPIRATORY-DISTRESS-SYNDROME
BLOOD MONONUCLEAR-CELLS
CRITICALLY-ILL PATIENTS
METABOLIC DYSFUNCTION
OXIDATIVE STRESS
DIPEPTIDE FORMS
SKELETAL-MUSCLE
GENE-EXPRESSION
11 Medical And Health Sciences
Publication Status
Published