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J Clin Endocrinol Metab. 2017 May 1;102(5):1712-1718. doi: 10.1210/jc.2016-3931.

Interleukin-1 Antagonism Decreases Cortisol Levels in Obese Individuals.

Author information

1
Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, CH-4031 Basel, Switzerland.
2
Department of Clinical Research, University Hospital Basel, CH-4031 Basel, Switzerland.
3
Department of Endocrinology, Medical University Clinic, Kantonsspital Aarau, CH-5001 Aarau, Switzerland.

Abstract

Context:

Increased cortisol levels in obesity may contribute to the associated metabolic syndrome. In obesity, the activated innate immune system leads to increased interleukin (IL)-1β, which is known to stimulate the release of adrenocorticotropin hormone (ACTH).

Objectives:

We hypothesized that in obesity IL-1 antagonism would result in downregulation of the hypothalamo-pituitary-adrenal axis, leading to decreased cortisol levels.

Design and Participants:

In this prospective intervention study, we included 73 patients with obesity (body mass index [BMI] ≥30 kg/m2) and at least one additional feature of the metabolic syndrome.

Outcome Measures:

The primary end point was change in morning cortisol from baseline to after the administration of the IL-1 receptor antagonist (anakinra/Kineret®, total dose 3 × 100 mg). Secondary end points were effects on salivary cortisol and ACTH.

Results:

Median age was 56 years, 50.7% of patients were female, and median BMI was 36.3 kg/m2. Median morning serum cortisol levels (nmol/L) decreased significantly after IL-1 antagonism [from baseline, 452 to 423; absolute difference, -38.7; 95% confidence interval (CI), -64 to -13.4; P = 0.0019]. Similar effects were found for salivary cortisol levels (-2.8; 95% CI, -4.4 to -1.3; P = 0.0007), ACTH levels (-2.2; 95% CI; -4.2 to -0.1; P = 0.038), systolic blood pressure (-5.2, 95% CI, -8.5 to -1.8; P = 0.0006), and heart rate (-2.9; 95% CI, -4.7 to -1.0; P = 0.0029).

Conclusion:

IL-1 antagonism in obese individuals with features of the metabolic syndrome leads to a decrease in serum cortisol, salivary cortisol, and ACTH levels along with a reduction in systolic blood pressure and heart rate.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT02227420.

PMID:
28324042
DOI:
10.1210/jc.2016-3931
[Indexed for MEDLINE]

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