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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.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.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.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 publication

DOI

10.1136/annrheumdis-2013-203926

Type

Journal article

Journal

Annals of the rheumatic diseases

Publication Date

02/2015

Volume

74

Pages

464 - 469

Addresses

Rheumatology Research Group, University of Birmingham, Birmingham, UK Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham, Birmingham, UK.

Keywords

Humans, Arthritis, Psoriatic, Arthritis, Rheumatoid, Hydrocortisone, Tumor Necrosis Factor-alpha, Immunoglobulin G, Receptors, Tumor Necrosis Factor, Antirheumatic Agents, Antibodies, Monoclonal, Adult, Aged, Middle Aged, Female, Male, Gas Chromatography-Mass Spectrometry, Infliximab, Etanercept