Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2009 Jul;64(7):723-30.
doi: 10.1093/gerona/glp046. Epub 2009 Apr 17.

Age-associated Increase in Cytokine Production During Systemic Inflammation: Adipose Tissue as a Major Source of IL-6

Affiliations
Free PMC article
Comparative Study

Age-associated Increase in Cytokine Production During Systemic Inflammation: Adipose Tissue as a Major Source of IL-6

Marlene E Starr et al. J Gerontol A Biol Sci Med Sci. .
Free PMC article

Abstract

Increased mortality and overexpression of interleukin-6 (IL-6) during inflammatory stress are well-documented age-associated phenomena; however, the site of IL-6 overexpression is not entirely known. Here, we report that white adipose tissue is a major source of IL-6 in aged animals during lipopolysaccharide (LPS)-induced systemic inflammation. Among the various tissues examined, white adipose tissue from the epididymal fat pad (located in the abdominal cavity) expressed the highest level of IL-6 messenger RNA in both young and aged mice with a 5.5-fold higher level in the aged. Immunohistochemistry revealed that, within the adipose tissue, LPS-induced IL-6 expression is localized to both the adipocytes and stromal cells. Compared with age-matched wild-type mice, aged IL-6((-/-)) mice exhibited reduced mortality to LPS suggesting a deleterious effect of IL-6 overexpression in the aged. These results demonstrate that increased vulnerability to systemic inflammation with age is due in part, to augmented IL-6 production by the adipose tissue.

Figures

Figure 1.
Figure 1.
Tissue distribution of lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) gene expression. Systemic inflammation was induced in young (6–7 mos old) and aged (22–27 mos old) C57BL/6 male mice by LPS injection (2.5 mg/kg, intraperitoneal) and mice were sacrificed 6 h later. All lanes are in a single gel. (A) RNA was isolated from various tissues of young and aged mice and analyzed by Northern blotting. Each lane represents pooled RNA samples from three mice. (B) Densitometric analysis of short exposure from (A). The shorter exposure was used because the bands for heart and fat appear to be saturated in the longer exposed autoradiograph. Young (open bars) and aged (closed bars). Total intensity of each band was normalized to 18S levels. The normalized IL-6 messenger RNA level in aged mouse fat was set at 1.0.
Figure 2.
Figure 2.
Lipopolysaccharide (LPS)-mediated expression of interleukin-6 (IL-6) in adipose tissue increases with age and correlates with severity of systemic inflammation. Systemic inflammation was induced in young (4–7 mos old) and aged (18–27 mos old) C57BL/6 male mice by LPS injection (2.5 mg/kg, intraperitoneal). (A) RNA was isolated from the epididymal adipose tissue of noninjected controls and mice sacrificed at 6 h after injection and analyzed by Northern blotting. Each lane represents an individual RNA sample from a single mouse. Lane 1: young control mouse without LPS injection; Lane 2: aged control mouse without LPS injection; Lanes 3–7: young mice with LPS injection; and Lanes 8–12: aged mice with LPS injection. (B) Densitometric analysis of (A): young (open bars) and aged (closed bars). Total intensity of each band was normalized to 18S levels. The average normalized IL-6 messenger RNA level in aged mouse fat was set at 1.0. (C) Plasma IL-6 levels 6 h after LPS injection were measured by enzyme-linked immunosorbent assay: young (open bars) and aged (closed bars). (D) Body temperatures 6 h after LPS injection. (E) Body weight at the time of LPS injection (g). (F) Epididymal fat pad weight (mg) at the time of sacrifice. Data are expressed as the mean ± standard deviation, n = 5 each group: *p < .05 and ***p < .001.
Figure 3.
Figure 3.
Age-associated expression of interleukin-6 (IL-6) in various adipose tissue depots. Systemic inflammation was induced in young (4 mos old) and aged (22 mos old) C57BL/6 male mice by lipopolysaccharide injection (2.5 mg/kg, intraperitoneal). (A) RNA was isolated from the epididymal, perirenal, and subcutaneous adipose tissues of both young and aged mice sacrificed 6 h after injection and analyzed by Northern blotting. Each lane represents an individual RNA sample from a single mouse. (B) Densitometric analysis of (A): young (open bars) and aged (closed bars). Total intensity of each band was normalized to 18S levels. The average normalized IL-6 messenger RNA level in aged mouse epididymal fat was set at 1.0. Data are expressed as the mean ± standard deviation, n = 3 each group: *p < .05 and ***p < .001.
Figure 4.
Figure 4.
Immunohistochemical localization of interleukin-6 (IL-6) in the adipose tissue. Immunohistochemical analysis was performed to localize IL-6 protein in adipose tissue from aged C57BL/6 male mice after lipopolysaccharide (LPS) injection (2.5 mg/kg, intraperitoneal). Strong positive staining with anti-IL-6 antibody is seen in adipocytes (closed arrow heads), vascular endothelial cells (open arrow heads), and inflammatory cells (arrows) of white epididymal adipose tissue from mice injected with LPS (top middle panel). Strong positive staining is seen in brown perirenal adipose tissue (closed arrow heads) associated with the kidney (Kd, top right panel), but not in vascular endothelial cells of the blood vessels (BV) in mice injected with LPS.
Figure 5.
Figure 5.
Aged interleukin-6 (IL-6) knockout mice are more resistant to lipopolysaccharide (LPS)-induced endotoxemia. Survival of IL-6(–/–) (closed squares) and wild-type control mice (open diamonds) was monitored for 7 days after LPS injection (5 mg/kg, intraperitoneal). All mice were 26-month-old females with C57BL/6 genetic background (n = 8 each group).

Similar articles

See all similar articles

Cited by 47 articles

See all "Cited by" articles

Publication types

Feedback