INCREASED PRODUCTION OF TUMOR-NECROSIS-FACTOR AND INTERLEUKIN-6 BY ARTERIAL-WALL OF AGED RATS

Plasma cytokine levels are enhanced in aged animals and in elderly people. Vascular cells are known to be both targets and sources of cytokines. To investigate the effect of aging on vascular cytokine synthesis, we studied tumor necrosis factor (TNF), interleukin-6 (IL-6), and prostacyclin (PGI(2)) production by the arterial wall using organoid culture of aorta from 10- (n = 8) and 30-mo-old (n = 8) rats, after activation by lipopolysaccharide (LPS). Biological activity of TNF and IL-6 was measured in supernatant from incubated vessels. 6-Ketoprostaglandin F-1 alpha (6-keto-PGF(1 alpha)), a stable metabolite of PGI(2), a secondary inflammatory mediator, was measured using enzyme immunoassay. In the absence of LPS, TNF production was undetectable in most animals and was not significantly increased in the aged group. By contrast IL-6 and 6-keto-PGF(1 alpha) productions, in the absence of LPS, were significantly greater in 30- (8,140 : 1,350 U/mu g DNA and 23.2 +/- 6.4 ng/mu g DNA, respectively) than in 10-mo animals (3,060 +/- 350 U/mu g DNA and 8.4 +/- 1.6 ng/mu g DNA, P < 0.01 and P < 0.05, respectively). LPS-induced production of TNF, IL-6, and 6-keto-PGF(1 alpha) was significantly increased in old rats, being increased respectively by 3.2-, 3.5-, and 2.4-fold at 1 ng/ml LPS, compared with the production in young rats. Because TNF and IL-6 are capable of regulating vascular cell function such as proliferation protein synthesis and contractility, these cytokines might play a major role in age-related remodeling of arteries and age-related vascular diseases.