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.Research output: Contribution to journal › Article › peer-review
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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 -