4.3 Article

Effects of interleukin-1 antagonism on cortisol levels in individuals with obesity: a randomized clinical trial

期刊

ENDOCRINE CONNECTIONS
卷 8, 期 6, 页码 701-708

出版社

BIOSCIENTIFICA LTD
DOI: 10.1530/EC-19-0201

关键词

metabolic syndrome; inflammation; interleukin-1; HPA axis; anakinra

资金

  1. Swiss National Foundation [PP00P3-12346]
  2. 'Wissenschaftspool' of the University Hospital Basel
  3. University of Basel (Nachwuchsfoerderung 2017)
  4. 'Young Talents in Clinical Research' program by the Bangerter Foundation
  5. Swiss Academy of Medical Sciences (SAMS)

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Background: Anti-inflammatory treatment with interleukin-1 (IL-1) antagonism decreases both cortisol and adrenocorticotropin hormone (ACTH) levels in individuals with obesity in short term. However, it remains unknown whether these effects persist upon prolonged treatment. Methods: In this double-blind, parallel-group trial involving patients with features of the metabolic syndrome, 33 patients were randomly assigned to receive 100 mg of anakinra (recombinant human IL-1 receptor antagonist) subcutaneously twice-daily and 34 patients to receive placebo for 4 weeks. For this analysis, change in cortisol and ACTH levels from baseline to 4 weeks were predefined end points of the trial. Results: The mean age was 54 years, baseline cortisol levels were 314 nmol/L (IQR 241-385) and C-reactive protein (CRP) levels were 3.4 mg/L (IQR 1.7-4.8). Treatment with anakinra led to a significant decrease in cortisol levels at day 1 when compared to placebo with an adjusted between-group difference of 28 nmol/L (95% CI, -7 to -43; P = 0.03). After 4 weeks, the cortisol-lowering effect of anakinra was attenuated and overall was statistically not significant (P = 0.72). Injection-site reactions occurred in 21 patients receiving anakinra and were associated with higher CRP and cortisol levels. Conclusions: IL-1 antagonism decreases cortisol levels in male patients with obesity and chronic low-grade inflammation on the short term. After prolonged treatment, this effect is attenuated, probably due to injection-site reactions.

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