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.
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.
authors.affiliation: Department of Surgery.
authors.forename: Marlene E
authors.initials: ME
authors.lastname: Starr
authors.affiliation: Markey Cancer Center, and.
authors.forename: Mizuki
authors.initials: M
authors.lastname: Saito
authors.affiliation: Department of Surgery, Markey Cancer Center, and.
authors.forename: B Mark
authors.initials: BM
authors.lastname: Evers
authors.affiliation: Department of Surgery, Markey Cancer Center, and Department of Physiology, University of Kentucky, Lexington. hiroshi.saito@uky.edu.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saito
mesh_terms: D000273:Adipose Tissue / Q000276:immunology*; D000367:Age Factors; D000818:Animals; D007249:Inflammation / Q000276:immunology*; D053583:Interleukin-1beta / Q000502:physiology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015854:Up-Regulation
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6
keywords: Adipose tissue; Aging; IL-1β; IL-6; Inflammation; Sepsis