ABSTRACT
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-PGF(1alpha) (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 Subject(s)
Adipose Tissue, White/metabolism
, Aspirin/administration & dosage
, Cyclooxygenase Inhibitors/administration & dosage
, Interleukin-6/metabolism
, Obesity/metabolism
, Adipocytes/metabolism
, Aged
, Animals
, Aspirin/pharmacology
, Case-Control Studies
, Cyclooxygenase Inhibitors/pharmacology
, Female
, Gonads/metabolism
, Humans
, Male
, Mice
, Mice, Obese
, Middle Aged
, Prostaglandin-Endoperoxide Synthases/metabolism
, Receptors, Prostaglandin/metabolism
, Subcutaneous Fat/metabolism
, Tumor Necrosis Factor-alpha/blood