Interleukin‐10 Protects Against Vascular Dysfunction with Aging

Abstract

Aging produces vascular inflammation and dysfunction in blood vessels. We tested the hypothesis that interleukin‐10 (IL‐10), a potent anti‐inflammatory cytokine, protects against aging‐induced vascular dysfunction. Responses of carotid arteries from young (7‐8 mo) and old (19‐20 mo) wild‐type and IL‐10 deficient mice (IL‐10‐/‐) were examined in vitro. In arteries from wild‐type mice, acetylcholine (an endothelium‐dependent agonist) produced relaxation that was not altered at this age. In contrast, relaxation to acetylcholine in arteries from IL‐10 deficient mice was markedly impaired with age. For example, relaxation of the carotid artery to 10 μmol/L acetylcholine was 87±3 and 48±2% in old wild‐type versus old IL‐10 deficient mice, respectively (P<0.01). Tempol (1 mM), a scavenger of superoxide, did not affect responses in young or old wild‐type or young IL‐10 deficient mice, but restored vasodilation to acetylcholine to normal in old IL‐10 deficient mice. Relaxation of the carotid artery to nitroprusside was not altered in any group. These findings provide the first evidence that age‐related and superoxide‐mediated endothelial dysfunction occurred much earlier and to a greater extent with IL‐10 deficiency. Our findings suggest a novel role for IL‐10 in oxidative stress and age‐related vascular dysfunction.