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

Ogston, N.C., Karastergiou, K., Hosseinzadeh-Attar, M.J., Bhome, R., Madani, R., Stables, M., Gilroy, D., Flachs, P., Hensler, M., Kopecky, J. and Mohamed-Ali, V. (2008) Low-dose acetylsalicylic acid inhibits the secretion of interleukin-6 from white adipose tissue. International Journal of Obesity, 32 (12), 1807-1815. (doi:10.1038/ijo.2008.190).

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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Contributors

Author: R. Bhome

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