TNF regulates cortisol metabolism in vivo in patients with inflammatory arthritis

Nanus, D.E., Filer, A.D., Hughes, B., Fisher, B.A., Taylor, P.C., Stewart, P.M., Buckley, C.D., McInnes, I. , Cooper, M.S. and Raza, K. (2015) TNF regulates cortisol metabolism in vivo in patients with inflammatory arthritis. Annals of the Rheumatic Diseases, 74(2), pp. 464-469. (doi:10.1136/annrheumdis-2013-203926)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain
Authors: Nanus, D.E., Filer, A.D., Hughes, B., Fisher, B.A., Taylor, P.C., Stewart, P.M., Buckley, C.D., McInnes, I., Cooper, M.S., and Raza, K.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Annals of the Rheumatic Diseases
Publisher:BMJ Publishing Group
ISSN:0003-4967
ISSN (Online):1468-2060
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