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

Department of Clinical Medicine

3 Citations (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.

Original language	English
Journal	Stress: The International Journal on the Biology of Stress
Volume	20
Issue number	2
Pages (from-to)	183-188
ISSN	1025-3890
DOIs	https://doi.org/10.1080/10253890.2017.1292420
Publication status	Published - 2017

Keywords

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

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10.1080/10253890.2017.1292420

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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.

In: Stress: The International Journal on the Biology of Stress , Vol. 20, No. 2, 2017, p. 183-188.

Research output: Contribution to journal › Journal article › Research › peer-review

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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.",

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AU - Lewis, John Goodwyn

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AU - Møller, Kirsten

AU - Torpy, David James

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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.

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

Abstract

Keywords

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