TNFα regulates cortisol metabolism in vivo in patients with inflammatory arthritis

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TNFα regulates cortisol metabolism in vivo in patients with inflammatory arthritis. / Nanus, Dominika E; Filer, Andrew D; Hughes, Beverly; Fisher, Benjamin A; Taylor, Peter C; Stewart, Paul M; Buckley, Christopher D; McInnes, Iain; Cooper, Mark S; Raza, Karim.

In: Annals of the Rheumatic Diseases, Vol. 74, 02.01.2014, p. 464-469.

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@article{1913ac280be44ea786fa0fc90a1057c4,
title = "TNFα regulates cortisol metabolism in vivo in patients with inflammatory arthritis",
abstract = "OBJECTIVE: To determine the relationship between inflammation and glucocorticoid metabolism in vivo, in a clinical study of patients with inflammatory arthritis treated with anti-TNFα therapy.METHODS: Urine samples were collected from patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) as part of a multicentre study assessing responses to infliximab and etanercept. Systemic measures of glucocorticoid metabolism were assessed by gas chromatography/mass spectrometry at weeks 0 (baseline), 4 and 12 after anti-TNFα therapy. Clinical data including DAS28 and C-reactive protein were also collected.RESULTS: Systemic measures of 11β-HSD1 activity in patients with inflammatory arthritis decreased significantly following anti-TNFα therapy in patients with RA and PsA. Additionally, the activity of the glucocorticoid inactivating enzyme 5α-reductase appeared to increase significantly.CONCLUSIONS: This study demonstrates, for the first time, that the increased 11β-HSD1 activity seen in patients with inflammatory arthritis is mediated through TNFα. Furthermore, the changes in related glucocorticoid metabolising enzymes suggest that there is a coordinated change in glucocorticoid metabolism which promotes higher tissue glucocorticoid levels.",
author = "Nanus, {Dominika E} and Filer, {Andrew D} and Beverly Hughes and Fisher, {Benjamin A} and Taylor, {Peter C} and Stewart, {Paul M} and Buckley, {Christopher D} and Iain McInnes and Cooper, {Mark S} and Karim Raza",
year = "2014",
month = jan,
day = "2",
doi = "10.1136/annrheumdis-2013-203926",
language = "English",
volume = "74",
pages = "464--469",
journal = "Annals of the Rheumatic Diseases",
issn = "0003-4967",
publisher = "BMJ Publishing Group",

}

RIS

TY - JOUR

T1 - TNFα regulates cortisol metabolism in vivo in patients with inflammatory arthritis

AU - Nanus, Dominika E

AU - Filer, Andrew D

AU - Hughes, Beverly

AU - Fisher, Benjamin A

AU - Taylor, Peter C

AU - Stewart, Paul M

AU - Buckley, Christopher D

AU - McInnes, Iain

AU - Cooper, Mark S

AU - Raza, Karim

PY - 2014/1/2

Y1 - 2014/1/2

N2 - OBJECTIVE: To determine the relationship between inflammation and glucocorticoid metabolism in vivo, in a clinical study of patients with inflammatory arthritis treated with anti-TNFα therapy.METHODS: Urine samples were collected from patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) as part of a multicentre study assessing responses to infliximab and etanercept. Systemic measures of glucocorticoid metabolism were assessed by gas chromatography/mass spectrometry at weeks 0 (baseline), 4 and 12 after anti-TNFα therapy. Clinical data including DAS28 and C-reactive protein were also collected.RESULTS: Systemic measures of 11β-HSD1 activity in patients with inflammatory arthritis decreased significantly following anti-TNFα therapy in patients with RA and PsA. Additionally, the activity of the glucocorticoid inactivating enzyme 5α-reductase appeared to increase significantly.CONCLUSIONS: This study demonstrates, for the first time, that the increased 11β-HSD1 activity seen in patients with inflammatory arthritis is mediated through TNFα. Furthermore, the changes in related glucocorticoid metabolising enzymes suggest that there is a coordinated change in glucocorticoid metabolism which promotes higher tissue glucocorticoid levels.

AB - OBJECTIVE: To determine the relationship between inflammation and glucocorticoid metabolism in vivo, in a clinical study of patients with inflammatory arthritis treated with anti-TNFα therapy.METHODS: Urine samples were collected from patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) as part of a multicentre study assessing responses to infliximab and etanercept. Systemic measures of glucocorticoid metabolism were assessed by gas chromatography/mass spectrometry at weeks 0 (baseline), 4 and 12 after anti-TNFα therapy. Clinical data including DAS28 and C-reactive protein were also collected.RESULTS: Systemic measures of 11β-HSD1 activity in patients with inflammatory arthritis decreased significantly following anti-TNFα therapy in patients with RA and PsA. Additionally, the activity of the glucocorticoid inactivating enzyme 5α-reductase appeared to increase significantly.CONCLUSIONS: This study demonstrates, for the first time, that the increased 11β-HSD1 activity seen in patients with inflammatory arthritis is mediated through TNFα. Furthermore, the changes in related glucocorticoid metabolising enzymes suggest that there is a coordinated change in glucocorticoid metabolism which promotes higher tissue glucocorticoid levels.

U2 - 10.1136/annrheumdis-2013-203926

DO - 10.1136/annrheumdis-2013-203926

M3 - Article

C2 - 24385202

VL - 74

SP - 464

EP - 469

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

SN - 0003-4967

ER -