Pyrexia's effect on the CBG-cortisol thermocouple, rather than CBG cleavage, elevates the acute free cortisol response to TNF-α in humans

Marni Anne Nenke; Signe Tellerup Nielsen; Louise Lang Lehrskov; John Goodwyn Lewis; Wayne Rankin; Kirsten Møller; David James Torpy

doi:10.1080/10253890.2017.1292420

Pyrexia's effect on the CBG-cortisol thermocouple, rather than CBG cleavage, elevates the acute free cortisol response to TNF-α in humans

Marni Anne Nenke, Signe Tellerup Nielsen, Louise Lang Lehrskov, John Goodwyn Lewis, Wayne Rankin, Kirsten Møller, David James Torpy

Institut for Klinisk Medicin

3 Citationer (Scopus)

Abstract

Corticosteroid-binding globulin (CBG) cleavage promotes local cortisol delivery in inflammation. Enzymatic cleavage of high-affinity CBG to low-affinity CBG (haCBG to laCBG) occurs at inflammatory sites and is now measurable in vivo; however, the time kinetics of haCBG depletion following an inflammatory stimulus is unknown. Hence our aim was to determine the immediate effect of the key pro-inflammatory cytokine TNF-α on CBG levels and cleavage. We performed a crossover study of 12 healthy males receiving a TNF-α versus saline infusion, measuring total CBG, haCBG, laCBG and free and total cortisol hourly for 6 h. There was no change in total CBG or haCBG levels in the first 6 h of inflammation between the groups, suggesting that CBG cleavage is not activated nor is hepatic CBG production affected by TNF-α in this time frame. There was an early increase in the ratio of free:total cortisol, in association with pyrexia. This accords with data indicating that CBG acts a thermocouple in vivo, increasing free cortisol levels independent of elastase-driven cleavage.

Originalsprog	Engelsk
Tidsskrift	Stress: The International Journal on the Biology of Stress
Vol/bind	20
Udgave nummer	2
Sider (fra-til)	183-188
ISSN	1025-3890
DOI	https://doi.org/10.1080/10253890.2017.1292420
Status	Udgivet - 2017

Adgang til dokumentet

10.1080/10253890.2017.1292420

Citationsformater

Nenke, M. A., Nielsen, S. T., Lehrskov, L. L., Lewis, J. G., Rankin, W., Møller, K., & Torpy, D. J. (2017). Pyrexia's effect on the CBG-cortisol thermocouple, rather than CBG cleavage, elevates the acute free cortisol response to TNF-α in humans. Stress: The International Journal on the Biology of Stress , 20(2), 183-188. https://doi.org/10.1080/10253890.2017.1292420

Pyrexia's effect on the CBG-cortisol thermocouple, rather than CBG cleavage, elevates the acute free cortisol response to TNF-α in humans. / Nenke, Marni Anne; Nielsen, Signe Tellerup; Lehrskov, Louise Lang et al.

I: Stress: The International Journal on the Biology of Stress , Bind 20, Nr. 2, 2017, s. 183-188.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

@article{f5695fdcc9614bee833400932258b2cd,

title = "Pyrexia's effect on the CBG-cortisol thermocouple, rather than CBG cleavage, elevates the acute free cortisol response to TNF-α in humans",

abstract = "Corticosteroid-binding globulin (CBG) cleavage promotes local cortisol delivery in inflammation. Enzymatic cleavage of high-affinity CBG to low-affinity CBG (haCBG to laCBG) occurs at inflammatory sites and is now measurable in vivo; however, the time kinetics of haCBG depletion following an inflammatory stimulus is unknown. Hence our aim was to determine the immediate effect of the key pro-inflammatory cytokine TNF-α on CBG levels and cleavage. We performed a crossover study of 12 healthy males receiving a TNF-α versus saline infusion, measuring total CBG, haCBG, laCBG and free and total cortisol hourly for 6 h. There was no change in total CBG or haCBG levels in the first 6 h of inflammation between the groups, suggesting that CBG cleavage is not activated nor is hepatic CBG production affected by TNF-α in this time frame. There was an early increase in the ratio of free:total cortisol, in association with pyrexia. This accords with data indicating that CBG acts a thermocouple in vivo, increasing free cortisol levels independent of elastase-driven cleavage.",

keywords = "Adult, Cross-Over Studies, Fever/metabolism, Humans, Hydrocortisone/blood, Inflammation/blood, Male, Transcortin/metabolism, Tumor Necrosis Factor-alpha/pharmacology, Young Adult",

author = "Nenke, {Marni Anne} and Nielsen, {Signe Tellerup} and Lehrskov, {Louise Lang} and Lewis, {John Goodwyn} and Wayne Rankin and Kirsten M{\o}ller and Torpy, {David James}",

year = "2017",

doi = "10.1080/10253890.2017.1292420",

language = "English",

volume = "20",

pages = "183--188",

journal = "Stress: The International Journal on the Biology of Stress ",

issn = "1025-3890",

publisher = "Taylor & Francis",

number = "2",

}

TY - JOUR

T1 - Pyrexia's effect on the CBG-cortisol thermocouple, rather than CBG cleavage, elevates the acute free cortisol response to TNF-α in humans

AU - Nenke, Marni Anne

AU - Nielsen, Signe Tellerup

AU - Lehrskov, Louise Lang

AU - Lewis, John Goodwyn

AU - Rankin, Wayne

AU - Møller, Kirsten

AU - Torpy, David James

PY - 2017

Y1 - 2017

N2 - Corticosteroid-binding globulin (CBG) cleavage promotes local cortisol delivery in inflammation. Enzymatic cleavage of high-affinity CBG to low-affinity CBG (haCBG to laCBG) occurs at inflammatory sites and is now measurable in vivo; however, the time kinetics of haCBG depletion following an inflammatory stimulus is unknown. Hence our aim was to determine the immediate effect of the key pro-inflammatory cytokine TNF-α on CBG levels and cleavage. We performed a crossover study of 12 healthy males receiving a TNF-α versus saline infusion, measuring total CBG, haCBG, laCBG and free and total cortisol hourly for 6 h. There was no change in total CBG or haCBG levels in the first 6 h of inflammation between the groups, suggesting that CBG cleavage is not activated nor is hepatic CBG production affected by TNF-α in this time frame. There was an early increase in the ratio of free:total cortisol, in association with pyrexia. This accords with data indicating that CBG acts a thermocouple in vivo, increasing free cortisol levels independent of elastase-driven cleavage.

AB - Corticosteroid-binding globulin (CBG) cleavage promotes local cortisol delivery in inflammation. Enzymatic cleavage of high-affinity CBG to low-affinity CBG (haCBG to laCBG) occurs at inflammatory sites and is now measurable in vivo; however, the time kinetics of haCBG depletion following an inflammatory stimulus is unknown. Hence our aim was to determine the immediate effect of the key pro-inflammatory cytokine TNF-α on CBG levels and cleavage. We performed a crossover study of 12 healthy males receiving a TNF-α versus saline infusion, measuring total CBG, haCBG, laCBG and free and total cortisol hourly for 6 h. There was no change in total CBG or haCBG levels in the first 6 h of inflammation between the groups, suggesting that CBG cleavage is not activated nor is hepatic CBG production affected by TNF-α in this time frame. There was an early increase in the ratio of free:total cortisol, in association with pyrexia. This accords with data indicating that CBG acts a thermocouple in vivo, increasing free cortisol levels independent of elastase-driven cleavage.

KW - Adult

KW - Cross-Over Studies

KW - Fever/metabolism

KW - Humans

KW - Hydrocortisone/blood

KW - Inflammation/blood

KW - Male

KW - Transcortin/metabolism

KW - Tumor Necrosis Factor-alpha/pharmacology

KW - Young Adult

U2 - 10.1080/10253890.2017.1292420

DO - 10.1080/10253890.2017.1292420

M3 - Journal article

C2 - 28166688

SN - 1025-3890

VL - 20

SP - 183

EP - 188

JO - Stress: The International Journal on the Biology of Stress

JF - Stress: The International Journal on the Biology of Stress

IS - 2

ER -

Pyrexia's effect on the CBG-cortisol thermocouple, rather than CBG cleavage, elevates the acute free cortisol response to TNF-α in humans

Abstract

Adgang til dokumentet

Fingeraftryk

Citationsformater