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- Title
Age-Associated Increase in Cytokine Production During Systemic Inflammation-II: The Role of IL-1β in Age-Dependent IL-6 Upregulation in Adipose Tissue.
- Authors
Starr, Marlene E.; Mizuki Saito; Evers, B. Mark; Hiroshi Saito; Saito, Mizuki; Saito, Hiroshi
- 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.
- Subjects
CYTOKINES; INFLAMMATION; INTERLEUKIN-1; INTERLEUKIN-6; ADIPOSE tissues; SEPSIS; AGING; AUTOCRINE mechanisms; AGE distribution; ANIMAL experimentation; BIOCHEMISTRY; INTERLEUKINS; PHENOMENOLOGY; MICE; RESEARCH funding
- Publication
Journals of Gerontology Series A: Biological Sciences & Medical Sciences, 2015, Vol 70, Issue 12, p1508
- ISSN
1079-5006
- Publication type
journal article
- DOI
10.1093/gerona/glu197