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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.

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