Interleukin-1 Antagonism Decreases Cortisol Levels in Obese Individuals

• Published in: The journal of clinical endocrinology and metabolism 2017-05, Vol.102 (5), p.1712-1718
• Main Authors: Urwyler, Sandrine Andrea, Schuetz, Philipp, Ebrahimi, Fahim, Donath, Marc Y, Christ-Crain, Mirjam
• Format: Article
• Language: English
• Subjects: Adrenal glands; Adrenocorticotropic hormone; Adrenocorticotropic Hormone - metabolism; Adrenocorticotropin (ACTH); Antirheumatic Agents - therapeutic use; Blood Pressure; Body mass; Body mass index; C-Reactive Protein - metabolism; Cortisol; Cytokines; Female; Follicle Stimulating Hormone - metabolism; Heart Rate; Hormones; Human Growth Hormone - metabolism; Humans; Hydrocortisone - metabolism; Hypothalamic-pituitary-adrenal axis; Immune system; Innate immunity; Interleukin 1; Interleukin 1 receptor antagonist; Interleukin 1 Receptor Antagonist Protein - therapeutic use; Interleukin-6 - metabolism; Luteinizing Hormone - metabolism; Male; Metabolic syndrome; Metabolic Syndrome - drug therapy; Metabolic Syndrome - metabolism; Middle Aged; Morning; Obesity; Obesity - drug therapy; Obesity - metabolism; Pituitary; Prolactin - metabolism; Prospective Studies; Saliva - chemistry; Thyrotropin - metabolism
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2016-3931

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