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J Gerontol A Biol Sci Med Sci. 2015 Dec;70(12):1508-15. doi: 10.1093/gerona/glu197. Epub 2014 Oct 24.

Age-Associated Increase in Cytokine Production During Systemic Inflammation-II: The Role of IL-1β in Age-Dependent IL-6 Upregulation in Adipose Tissue.

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Department of Surgery.
Markey Cancer Center, and.
Department of Surgery, Markey Cancer Center, and.
Department of Surgery, Markey Cancer Center, and Department of Physiology, University of Kentucky, Lexington.


Expression of interleukin-6 (IL-6) upon acute inflammatory stress is significantly augmented by aging in adipose tissue, a major source of this cytokine. In the present study, we examined the mechanism of age-dependent IL-6 overproduction using visceral white adipose tissue from C57BL/6 mice. Upon treatment with lipopolysaccharide (LPS) in vitro, IL-6 was produced by adipose tissue explants, and secreted levels were significantly higher in cultures from aged (24 months) mice compared to young (4 months). Interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNFα), two inducers of IL-6, were mainly produced by the lungs and spleen rather than adipose tissue in mice after LPS injection. Treatment of adipose explants with physiological levels of IL-1β induced significant age-dependent secretion of IL-6, while treatment with TNFα had little effect, demonstrating an augmented response of adipose tissues to IL-1β in the aged. In vitro experiments utilizing a neutralizing antibody against IL-1β and in vivo experiments utilizing IL-1-receptor-1 deficient mice, confirmed that IL-6 overproduction in the aged is regulated by autocrine/paracrine action of IL-1β which specifically occurs in aged adipose tissues. These findings indicate an elevated inflammatory potential of adipose tissue in the aged and a unique IL-1β-mediated mechanism for IL-6 overproduction, which may impact age-associated vulnerability to acute inflammatory diseases such as sepsis.


Adipose tissue; Aging; IL-1β; IL-6; Inflammation; Sepsis

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