Interleukin-10 protects against aging-induced endothelial dysfunction

Abstract

Carotid and cerebrovascular disease increase markedly with age contributing to stroke and cognitive impairment. Inflammation is a key element of vascular disease. In these studies, we tested the hypothesis that interleukin-10 (IL-10), a potent anti-inflammatory cytokine, protects against aging-induced endothelial dysfunction. Responses of carotid arteries from adult (5 ± 1 months) and old (22 ± 1 months) wild-type and IL-10-deficient mice were examined in vitro. Acetylcholine (an endothelium-dependent agonist) produced relaxation in arteries from adult wild-type that was not altered in old mice. In contrast, relaxation to acetylcholine in arteries from old IL-10-deficient mice was reduced by ∼50% (P < 0.05). Tempol, a scavenger of superoxide, did not affect responses in adult or old wild-type mice, but restored vasodilation to acetylcholine to normal in old IL-10-deficient mice. Responses of the carotid artery to nitroprusside (an endothelium-independent agonist) were not altered in any group. Vascular expression of IL-6 (a proinflammatory mediator of vascular disease) and components of NADPH oxidase (a major source of superoxide) was increased in old IL-10-deficient mice compared with wild-type (P < 0.05). These findings provide the first evidence that age-related and superoxide-mediated endothelial dysfunction occurs earlier with IL-10 deficiency. Our findings suggest a novel role for IL-10 to protect against age-related increases in expression of IL-6, oxidative stress, and endothelial dysfunction.

Depressed perivascular sensory innervation of mouse mesenteric arteries with advanced age

“…; Kinzenbaw et al . ) have found that ACh‐mediated vasodilatation is preserved in advanced age, impaired vasodilatations to ACh during ageing have been reported in rodents (Yang et al . ; Zhou et al .…”

Gestational food restriction decreases placental interleukin-10 expression and markers of autophagy and endoplasmic reticulum stress in murine intrauterine growth restriction

“…Treatment with recombinant IL10 rescues the pregnancy, seemingly via restoration of endovascular activity [40]. Outside of pregnancy, IL10 has also been implicated as a mediator of vascular protection in hypertension, diabetes and atherosclerosis [41-43]. Therefore, one interesting consequence of disordered IL10 seen in adverse pregnancy outcomes is that it may be involved in vascular remodeling seen in placental insufficiency and the developmental programming of cardiovascular disease seen in the offspring of pregnancies complicated by IUGR, preeclampsia, or prematurity.…”

Role of Interleukin-10 in Acute Brain Injuries

“…Old, but not young, IL-10 −/− mice have diminished vasodilatory responses to acetylcholine, while the nitroprusside response is intact, suggesting endothelial rather than vascular smooth muscle dysfunction (26). Additionally, viral transduction of canine basilar arteries with IL-10 increases vasodilatory responses and reduces levels of ICAM-1 and VCAM-1, further supporting the protective role of IL-10 on the endothelium (29).…”