Abstract
IntroductionImpairment in the ability of the inflamed synovium to generate cortisol has been proposed to be a factor in the persistence and severity of inflammatory arthritis. In the inflamed synovium, cortisol is generated from cortisone by the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme. The objective of this study was to determine the role of endogenous glucocorticoid metabolism in the development of persistent inflammatory arthritis.MethodsUrine samples were collected from patients with early arthritis (symptoms ≤12 weeks duration) whose final diagnostic outcomes were established after clinical follow-up and from patients with established rheumatoid arthritis (RA). All patients were free of disease-modifying anti-rheumatic drugs at the time of sample collection. Systemic measures of glucocorticoid metabolism were assessed in the urine samples by gas chromatography/mass spectrometry. Clinical data including CRP and ESR were also collected at baseline.ResultsSystemic measures of 11β-HSD1 activity were significantly higher in patients with early arthritis whose disease went on to persist, and also in the subgroup of patients with persistent disease who developed RA, when compared with patients whose synovitis resolved over time. We observed a significant positive correlation between systemic 11β-HSD1 activity and ESR/CRP in patients with established RA but not in any of the early arthritis patients group.ConclusionsThe present study demonstrates that patients with a new onset of synovitis whose disease subsequently resolved had significantly lower levels of systemic 11β-HSD1 activity when compared with patients whose synovitis developed into RA or other forms of persistent arthritis. Low absolute levels of 11β-HSD1 activity do not therefore appear to be a major contributor to the development of RA and it is possible that a high total body 11β-HSD1 activity during early arthritis may reduce the probability of disease resolution.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0633-2) contains supplementary material, which is available to authorized users.
Highlights
Impairment in the ability of the inflamed synovium to generate cortisol has been proposed to be a factor in the persistence and severity of inflammatory arthritis
Systemic measures of GC metabolism in patients with early arthritis in relation to clinical outcome and in patients with established rheumatoid arthritis (RA) In total, 75 patients were recruited to the study and had full clinical assessment and urinary corticosteroid analysis
This study shows that patients with a new onset of synovitis whose disease subsequently resolved had significantly lower levels of systemic 11β-HSD1 activity at presentation when compared with patients whose synovitis persisted
Summary
Impairment in the ability of the inflamed synovium to generate cortisol has been proposed to be a factor in the persistence and severity of inflammatory arthritis. The GC-activating capacity of synovial tissue explants (a reaction carried out by 11β-HSD1) has been shown to directly correlate with histological and clinical measures of inflammation in patients with established RA [4,5]. These patients have increased systemic measures of 11β-HSD1 activity that are significantly decreased upon treatment with anti-tumour necrosis factor alpha (TNFα) therapy [7]. This suggests that the observed upregulation of 11β-HSD1 in established RA can, at least partially, be explained by inflammation
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