Low-dose acetylsalicylic acid inhibits the secretion of interleukin-6 from white adipose tissue

• Published in: International Journal of Obesity Vol. 32; no. 12; pp. 1807 - 1815
• Main Authors: Ogston, N.C, Karastergiou, K, Hosseinzadeh-Attar, M.J, Bhome, R, Madani, R, Stables, M, Gilroy, D, Flachs, P, Hensler, M, Kopecky, J, Mohamed-Ali, V
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-12-2008; Nature Publishing Group
• Subjects: Adipocytes; Adipocytes - metabolism; Adipose tissue; Adipose Tissue, White - metabolism; Adipose tissues; Aged; Analysis; animal models; Animals; Aspirin; Aspirin - administration & dosage; Aspirin - pharmacology; Atherosclerosis; Biological and medical sciences; Body fat; Cardiovascular disease; Case-Control Studies; COX-2 inhibitors; Cyclooxygenase Inhibitors - administration & dosage; Cyclooxygenase Inhibitors - pharmacology; cyclooxygenase-2 inhibitors; Cytokines; Diabetes; Dosage and administration; Drug dosages; enzyme inhibition; enzyme inhibitors; Epidemiology; Fatty acids; Female; Gastrointestinal surgery; Gonads - metabolism; Health aspects; Health Promotion and Disease Prevention; Humans; Ingestion; Interleukin-6; Interleukin-6 - secretion; Internal Medicine; Male; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolism; Metabolites; Mice; Mice, Obese; Middle Aged; nonsteroidal anti-inflammatory agents; nutrition physiology; Obesity; Obesity - metabolism; obesity-related diseases; original-article; pathophysiology; Physiology; prostaglandin synthase; Prostaglandin-Endoperoxide Synthases - metabolism; prostaglandins; Public Health; Receptors, Prostaglandin - metabolism; secretion; Subcutaneous Fat - metabolism; Tumor Necrosis Factor-alpha - blood; University colleges; white adipose tissue; White people; United Kingdom; United Kingdom > UK; adipose tissue; prostaglandins; aspirin; prostacyclin; interleukin-6; Prostaglandin-endoperoxide synthase; Adipose tissue; Prostaglandin I2; Acetylsalicylic acid; Interleukin 6; Salicylates; Nutritional status; Obesity; White adipose tissue; Nutrition; Enzyme; Secretion; Low dose; Cytokine; Nutrition disorder; Enzyme inhibitor; Metabolic diseases; Antiplatelet agent; Non steroidal antiinflammatory agent; Analgesic; Antipyretic; Oxidoreductases
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/ijo.2008.190

Background: Chronically elevated interleukin-6 (IL-6) is implicated in obesity-associated pathologies, where a proportion of this cytokine is derived from adipose tissue. Proinflammatory prostaglandins, which regulate this cytokine elsewhere, are also produced by this tissue. Objective: To investigate whether constitutively active cyclooxygenase (COX)/prostaglandin (PG) pathway in white adipose tissue (WAT) is responsible for basal IL-6 production. Design: The effect of acetylsalicylic acid (ASA), an inhibitor of COX, on IL-6 was assessed in human subjects and mice. COX, downstream PG synthase (PGS) activity and PG receptor signalling were determined in subcutaneous (SC), gonadal (GN) WAT and adipocytes. Methods and Results: In obese humans, low-dose ASA (150 mg day-1 for 10 days) inhibited systemic IL-6 and reduced IL-6 release from SC WAT ex vivo (0.2 mM). Similarly, in mice, ASA (0.2 and 2.0 mg kg-1) suppressed SC WAT 6-keto-PGF1α (a stable metabolite of prostacyclin) and IL-6 release. Although both COX isoforms are comparably expressed, prostacyclin synthase expression is higher in GN WAT, with levels of activity correlating directly with IL-6. Both ASA (5 mM) and NS-398 (COX-2 selective inhibitor <or= 1 micromolar), but not SC-560 (COX-1 selective inhibitor <or= 1 micromolar), attenuated IL-6 release from murine WAT in vitro and abolished its depot differences. Prostacyclin receptor (IP) and, to a lesser extent, PGE2 (EP2 and EP4) receptor agonists elevated the release of IL-6 from adipocytes. Conclusions: In adipose tissue, constitutive COX-2-coupled prostacyclin triggers the release of basal IL-6, which in obese subjects is significantly dampened by ASA ingestion, thus offering a novel, modifiable pathway to regulate the potentially pathological component of this cytokine.