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 peo ple. Vascular cells are known to be both targets and sources of cytoki nes. To investigate the effect of aging on vascular cytokine synthesis , we studied tumor necrosis factor (TNF), interleukin-6 (IL-6), and pr ostacyclin (PGI(2)) production by the arterial wall using organoid cul ture of aorta from 10- (n = 8) and 30-mo-old (n = 8) rats, after activ ation by lipopolysaccharide (LPS). Biological activity of TNF and IL-6 was measured in supernatant from incubated vessels. 6-Ketoprostagland in F-1 alpha (6-keto-PGF(1 alpha)), a stable metabolite of PGI(2), a s econdary inflammatory mediator, was measured using enzyme immunoassay. In the absence of LPS, TNF production was undetectable in most animal s and was not significantly increased in the aged group. By contrast I L-6 and 6-keto-PGF(1 alpha) productions, in the absence of LPS, were s ignificantly 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 si gnificantly 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 ce ll 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.