Age-associated increase in cytokine production during systemic inflammation: adipose tissue as a major source of IL-6.
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.
Starr
Marlene E
ME
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, 77555-0828, USA.
Evers
B Mark
BM
Saito
Hiroshi
H
D052438:Adipocytes, White / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism*; D000375:Aging / Q000378:metabolism*; D000465:Algorithms; D000818:Animals; D015152:Blotting, Northern; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism* / Q000401:mortality; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation
D015850:Interleukin-6; D012333:RNA, Messenger