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TNFα regulates cortisol metabolism in vivo in patients with inflammatory arthritis
  1. Dominika E Nanus1,2,
  2. Andrew D Filer1,3,
  3. Beverly Hughes2,
  4. Benjamin A Fisher1,3,
  5. Peter C Taylor4,
  6. Paul M Stewart2,
  7. Christopher D Buckley1,5,
  8. Iain McInnes6,
  9. Mark S Cooper2,7,
  10. Karim Raza1,5
  1. 1Rheumatology Research Group, University of Birmingham, Birmingham, UK
  2. 2Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham, Birmingham, UK
  3. 3Department of Rheumatology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
  4. 4Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK
  5. 5Department of Rheumatology, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK
  6. 6Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK
  7. 7Anzac Research Institute, Concord Repatriation General Hospital, University of Sydney, Sydney, Australia
  1. Correspondence to Professor Karim Raza, Rheumatology Research Group, Centre for Translational Inflammation Research, School of Immunity and Infection, College of Medical and Dental Sciences, The University of Birmingham, Birmingham B15 2TT, UK; k.raza{at}bham.ac.uk

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.

  • Rheumatoid Arthritis
  • Psoriatic Arthritis
  • Anti-TNF
  • Corticosteroids

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