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.
authors.affiliation: Rheumatology Research Group, University of Birmingham, Birmingham, UK Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham, Birmingham, UK.
authors.forename: Dominika E
authors.initials: DE
authors.lastname: Nanus
authors.affiliation: Rheumatology Research Group, University of Birmingham, Birmingham, UK Department of Rheumatology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Filer
authors.affiliation: Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham, Birmingham, UK.
authors.forename: Beverly
authors.initials: B
authors.lastname: Hughes
authors.affiliation: Rheumatology Research Group, University of Birmingham, Birmingham, UK Department of Rheumatology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Fisher
authors.affiliation: Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Taylor
authors.affiliation: Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham, Birmingham, UK.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Stewart
authors.affiliation: Rheumatology Research Group, University of Birmingham, Birmingham, UK Department of Rheumatology, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Buckley
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
authors.forename: Iain
authors.initials: I
authors.lastname: McInnes
authors.affiliation: Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham, Birmingham, UK Anzac Research Institute, Concord Repatriation General Hospital, University of Sydney, Sydney, Australia.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Cooper
authors.affiliation: Rheumatology Research Group, University of Birmingham, Birmingham, UK Department of Rheumatology, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK.
authors.forename: Karim
authors.initials: K
authors.lastname: Raza
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use; D015535:Arthritis, Psoriatic / Q000188:drug therapy / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism*; D000068800:Etanercept; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007074:Immunoglobulin G / Q000627:therapeutic use; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068800:Etanercept; D006854:Hydrocortisone
keywords: Anti-TNF; Corticosteroids; Psoriatic Arthritis; Rheumatoid Arthritis