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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.

Author information

1
Department of Surgery.
2
Markey Cancer Center, and.
3
Department of Surgery, Markey Cancer Center, and.
4
Department of Surgery, Markey Cancer Center, and Department of Physiology, University of Kentucky, Lexington. hiroshi.saito@uky.edu.

Abstract

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.

KEYWORDS:

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

PMID:
25344820
PMCID:
PMC4643612
DOI:
10.1093/gerona/glu197
[Indexed for MEDLINE]
Free PMC Article

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