Interleukin-1 Antagonism Decreases Cortisol Levels in Obese Individuals.
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.
Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, CH-4031 Basel, Switzerland.|Department of Clinical Research, University Hospital Basel, CH-4031 Basel, Switzerland.
Sandrine Andrea
SA
Urwyler
Department of Clinical Research, University Hospital Basel, CH-4031 Basel, Switzerland.|Department of Endocrinology, Medical University Clinic, Kantonsspital Aarau, CH-5001 Aarau, Switzerland.
Philipp
P
Schuetz
Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, CH-4031 Basel, Switzerland.|Department of Clinical Research, University Hospital Basel, CH-4031 Basel, Switzerland.
Fahim
F
Ebrahimi
Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, CH-4031 Basel, Switzerland.|Department of Clinical Research, University Hospital Basel, CH-4031 Basel, Switzerland.
Marc Y
MY
Donath
Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, CH-4031 Basel, Switzerland.|Department of Clinical Research, University Hospital Basel, CH-4031 Basel, Switzerland.
Mirjam
M
Christ-Crain
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001794:Blood Pressure; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D006339:Heart Rate; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000378:metabolism; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism; D011446:Prospective Studies; D012463:Saliva / Q000737:chemistry; D013972:Thyrotropin / Q000378:metabolism
D018501:Antirheumatic Agents; C508600:IL6 protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6; D019382:Human Growth Hormone; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013972:Thyrotropin; D002097:C-Reactive Protein; D006854:Hydrocortisone