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: Dominika E Nanus, Andrew D Filer, Beverly Hughes, Benjamin A Fisher, Peter C Taylor, Paul M Stewart, Christopher D Buckley, Iain McInnes, Mark S Cooper, Karim Raza
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 74 Issue 2 Pg. 464-9 (Feb 2015) ISSN: 1468-2060 [Electronic] England
• PMID: 24385202 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Chemical References

• Antibodies, Monoclonal
• Antirheumatic Agents
• Immunoglobulin G
• Receptors, Tumor Necrosis Factor
• Tumor Necrosis Factor-alpha
• Infliximab
• Etanercept
• Hydrocortisone

Topics

• Adult
• Aged
• Antibodies, Monoclonal (therapeutic use)
• Antirheumatic Agents (therapeutic use)
• Arthritis, Psoriatic (drug therapy, metabolism)
• Arthritis, Rheumatoid (drug therapy, metabolism)
• Etanercept
• Female
• Gas Chromatography-Mass Spectrometry
• Humans
• Hydrocortisone (metabolism)
• Immunoglobulin G (therapeutic use)
• Infliximab
• Male
• Middle Aged
• Receptors, Tumor Necrosis Factor (therapeutic use)
• Tumor Necrosis Factor-alpha (metabolism)