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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63 Scopus citations

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.

Original languageEnglish
Pages (from-to)1508-1515
Number of pages8
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume70
Issue number12
DOIs
StatePublished - Dec 2015

Bibliographical note

Publisher Copyright:
© 2015 The Author.

Keywords

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

ASJC Scopus subject areas

  • General Medicine

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