TNFα regulates cortisol metabolism in vivo in patients with inflammatory arthritis

Dominika E Nanus; Andrew D Filer; Beverly Hughes; Benjamin A Fisher; Peter C Taylor; Paul M Stewart; Christopher D Buckley; Iain McInnes; Mark S Cooper; Karim Raza

doi:10.1136/annrheumdis-2013-203926

TNFα regulates cortisol metabolism in vivo in patients with inflammatory arthritis

Dominika E Nanus, Andrew D Filer, Beverly Hughes, Benjamin A Fisher, Peter C Taylor, Paul M Stewart, Christopher D Buckley, Iain McInnes, Mark S Cooper, Karim Raza

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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.

Original language	English
Pages (from-to)	464-469
Journal	Annals of the Rheumatic Diseases
Volume	74
DOIs	https://doi.org/10.1136/annrheumdis-2013-203926
Publication status	Published - 2 Jan 2014

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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",

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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

SN - 0003-4967

VL - 74

SP - 464

EP - 469

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

ER -

TNFα regulates cortisol metabolism in vivo in patients with inflammatory arthritis

Abstract

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