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

International Journal of Obesity volume 32, pages 1807–1815 (2008)Cite this article

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-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 ⩽1 μM), but not SC-560 (COX-1 selective inhibitor ⩽1 μM), 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.

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Acknowledgements

This work was supported by a Wellcome Trust Collaborative Research Initiative Grant to VM-A and JK (The Wellcome Trust no. 070821/Z/03/Z), from the European Commission (LSHM-CT-2004-005272) and CRDC UCH Grant (award number 44505). MJH was supported by a clinical research fellowship from the Islamic Republic of Iran.

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Authors and Affiliations

  1. Adipokines and Metabolism Research Group, University College London, London, UK

    N C Ogston, K Karastergiou, M J Hosseinzadeh-Attar, R Bhome, R Madani & V Mohamed-Ali

  2. Division of Medicine, Centre for Clinical Pharmacology, University College London, London, UK

    M Stables & D Gilroy

  3. Department of Adipose Tissue Biology, Institute of Physiology, Academy of Sciences, Prague, Czech Republic

    P Flachs, M Hensler & J Kopecky

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  1. N C Ogston
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Correspondence to V Mohamed-Ali.

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Ogston, N., Karastergiou, K., Hosseinzadeh-Attar, M. et al. Low-dose acetylsalicylic acid inhibits the secretion of interleukin-6 from white adipose tissue. Int J Obes 32, 1807–1815 (2008). https://doi.org/10.1038/ijo.2008.190

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