Original Article

International Journal of Obesity (2008) 32, 1807–1815; doi:10.1038/ijo.2008.190; published online 4 November 2008

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

N C Ogston1, K Karastergiou1, M J Hosseinzadeh-Attar1, R Bhome1, R Madani1, M Stables2, D Gilroy2, P Flachs3, M Hensler3, J Kopecky3 and V Mohamed-Ali1

  1. 1Adipokines and Metabolism Research Group, University College London, London, UK
  2. 2Division of Medicine, Centre for Clinical Pharmacology, University College London, London, UK
  3. 3Department of Adipose Tissue Biology, Institute of Physiology, Academy of Sciences, Prague, Czech Republic

Correspondence: Dr V Mohamed-Ali, Adipokines and Metabolism Research Group, Division of Medicine, Centre for Clinical Pharmacology, University College London, 5 University Street, London WC1E 6JJ, UK. E-mail: rmhavma@ucl.ac.uk

Received 10 March 2008; Revised 30 April 2008; Accepted 31 August 2008; Published online 4 November 2008.

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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-PGF1alpha (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 less than or equal to1 muM), but not SC-560 (COX-1 selective inhibitor less than or equal to1 muM), 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.

Keywords:

interleukin-6, adipose tissue, prostaglandins, prostacyclin, aspirin

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