TNFα regulates cortisol metabolism in vivo in patients with inflammatory arthritis
TNFα regulates cortisol metabolism in vivo in patients with inflammatory arthritis
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DOI：
10.1136/annrheumdis-2013-203926
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发表时间：
2015-02-01
影响因子：
27.4
通讯作者：
Raza, Karim
中科院分区：
文献类型：
--
作者：
Nanus, Dominika E.;Filer, Andrew D.;Raza, Karim
目的探讨炎症与糖皮质激素代谢的关系，为临床应用抗肿瘤坏死因子α（TNF α）治疗炎症性关节炎（RA）和银屑病关节炎（PsA）患者提供实验依据。在抗TNF α治疗后第0周（基线）、第4周和第12周，通过气相色谱/质谱法评估糖皮质激素代谢的全身指标。临床数据，包括DAS 28和C-反应蛋白也collected.Results系统的措施，11 β-HSD 1活性在炎症性关节炎患者显着下降后，抗TNF α治疗RA和PsA患者。此外，糖皮质激素失活酶5 α-reductase的活性出现显着increasingsignificant.Conclusions这项研究表明，第一次，增加11 β-HSD 1活性的炎症性关节炎患者中看到的是通过TNF α介导的。此外，相关糖皮质激素代谢酶的变化表明，糖皮质激素代谢存在协调变化，促进组织糖皮质激素水平升高。
Objective To determine the relationship between inflammation and glucocorticoid metabolism in vivo, in a clinical study of patients with inflammatory arthritis treated with anti-TNF alpha 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-TNF alpha therapy. Clinical data including DAS28 and C-reactive protein were also collected.Results Systemic measures of 11 beta-HSD1 activity in patients with inflammatory arthritis decreased significantly following anti-TNF alpha therapy in patients with RA and PsA. Additionally, the activity of the glucocorticoid inactivating enzyme 5 alpha-reductase appeared to increase significantly.Conclusions This study demonstrates, for the first time, that the increased 11 beta-HSD1 activity seen in patients with inflammatory arthritis is mediated through TNF alpha. Furthermore, the changes in related glucocorticoid metabolising enzymes suggest that there is a coordinated change in glucocorticoid metabolism which promotes higher tissue glucocorticoid levels.