Background: 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). We therefore hypothesised that in obesity IL-1 antagonism would result in downregulation of the hypothalamo-pituitary-adrenal (HPA) axis, leading to decreased cortisol levels.
Methods: In this prospective intervention study we included 73 patients with obesity (BMI >30 kg/m2) and at least one additional feature of the metabolic syndrome. The primary endpoint 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 endpoints were effects on salivary cortisol and ACTH.
Results: Median morning serum cortisol levels (nmol/l) decreased significantly after IL-1-antagonism (from baseline 452 to 423, absolute difference −38.7, 95%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. IL-1 antagonism could thus be a novel treatment option to improve cortisol levels and associated comorbidities in obesity.
20 - 23 May 2017
European Society of Endocrinology