Increased production of tumor necrosis factor and interleukin-6 by
the arterial wall of aged rats.
Belmin, Jo[diaeresis]el, Catherine Bernard, Bruno Corman, R[acute]egine
Merval, Bruno Esposito, Alain Tedgui.
H[circumflex]opital de G[acute]erontologie Ren[acute]e Muret-Bigottini,
93270 Sevran, France, Institut National de la Sant[acute]e et de la Recherche
M[acute]edicale (INSERM), Unit[acute]e 141, and Institut F[acute]ederatif de
Recherche Circulation, H[circumflex]opital Lariboisi[grave]ere, 75010 Paris,
France, D[acute]epartement de Biologie Cellulaire et Mol[acute]eculaire,
C.E.N. Saclay, 92191 Gif-sur-Yvette, France.
APStracts 2:0036H, 1995.
Plasma cytokine levels are enhanced in aged animals and in the
elderly. 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 (PGI2) production by the arterial wall using
organoid culture of aorta from 10- (n=8) and 30-month (n=8) old rats,
after activation by lipopolysaccharide (LPS). Biological activity of
TNF and IL-6 was measured in supernatant from incubated vessels. 6
-keto-PGF1[alpha], a stable metabolite of PGI2, the secondary inflamatory
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-PGF1[alpha] productions, in the absence of LPS, were significantly
greater in 30- (8140 +/- 1350 U/[mu]g DNA and 23.2 +/- 6.4 ng/[mu]g DNA,
respectively) than in 10-month animals (3060 +/- 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-PGF1[alpha] was significantly increased
in old rats, being increased respectively by 3.2-, 3.5- and 2.4-fold
at 1 ng/ml LPS, as compared with the production in young rats. Since
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.
Received 27 June 1994; accepted in final form 10 January 1995.
APS Manuscript Number H560-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 February 1995.