title: Low-dose acetylsalicylic acid inhibits the secretion of interleukin-6 from white adipose tissue.
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.
  
  
  METHODS
  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.
  
  
  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 <or=1 microM), but not SC-560 (COX-1 selective inhibitor <or=1 microM), attenuated IL-6 release from murine WAT in vitro and abolished its depot differences. Prostacyclin receptor (IP) and, to a lesser extent, PGE(2) (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.
authors.affiliation: Adipokines and Metabolism Research Group, University College London, London, UK.
authors.forename: N C
authors.initials: NC
authors.lastname: Ogston
authors.forename: K
authors.initials: K
authors.lastname: Karastergiou
authors.forename: M J
authors.initials: MJ
authors.lastname: Hosseinzadeh-Attar
authors.forename: R
authors.initials: R
authors.lastname: Bhome
authors.forename: R
authors.initials: R
authors.lastname: Madani
authors.forename: M
authors.initials: M
authors.lastname: Stables
authors.forename: D
authors.initials: D
authors.lastname: Gilroy
authors.forename: P
authors.initials: P
authors.lastname: Flachs
authors.forename: M
authors.initials: M
authors.lastname: Hensler
authors.forename: J
authors.initials: J
authors.lastname: Kopecky
authors.forename: V
authors.initials: V
authors.lastname: Mohamed-Ali
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D052436:Adipose Tissue, White / Q000378:metabolism*; D000368:Aged; D000818:Animals; D001241:Aspirin / Q000008:administration & dosage* / Q000494:pharmacology; D016022:Case-Control Studies; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D006066:Gonads / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008820:Mice, Obese; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000378:metabolism; D050151:Subcutaneous Fat / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D016861:Cyclooxygenase Inhibitors; D015850:Interleukin-6; D011982:Receptors, Prostaglandin; D014409:Tumor Necrosis Factor-alpha; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin