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Diabetes 51:1931-1937, 2002
© 2002 by the American Diabetes Association, Inc.
Interleukin-10 Protects Nitric Oxide–Dependent Relaxation During Diabetes
Role of Superoxide
1 Department of Internal Medicine, University of Iowa College of Medicine and VA Medical Center, Iowa City, Iowa
2 Department of Pharmacology, University of Iowa College of Medicine and VA Medical Center, Iowa City, Iowa
Interleukin (IL)-10, an anti-inflammatory cytokine, preserves endothelial function during acute inflammation. We tested the hypotheses that IL-10 plays a protective role in blood vessels during diabetes by suppressing impairment of endothelium-dependent relaxation and that protection by IL-10 is mediated by effects on superoxide (O2-). Streptozotocin (150 mg/kg i.p.) or citrate buffer was injected into IL-10–deficient (IL-10-/-) mice and wild-type controls (IL-10+/+). In IL-10+/+ and IL-10-/- mice, blood glucose levels were 
120 mg/dl after citrate administration and 400 mg/dl after streptozotocin administration. Vasorelaxation was examined in arteries in vitro 12–16 weeks later. Maximum relaxation to acetylcholine (30 µmol/l) was 88 ± 3% (means ± SE) in nondiabetic mice and 84 ± 3% in diabetic IL-10+ /+ mice (P > 0.05). Thus, at this time point, diabetes did not impair endothelium-dependent relaxation in vessels in wild-type mice. In contrast, maximum relaxation in vessels from diabetic IL-10-/- mice was significantly decreased (74 ± 5%) compared with nondiabetic IL-10-/- mice (93 ± 2%, P < 0.05). Superoxide dismutase with polyethylene glycol (PEG-SOD) restored impaired responses to acetylcholine to levels seen in controls. Responses to acetylcholine also were improved by allopurinol (an inhibitor of xanthine oxidase) in vessels from diabetic IL-10- /- mice. Thus, diabetes produces greater impairment of relaxation to acetylcholine in IL-10-/- mice than in IL-10+/ + mice. These findings provide direct evidence that IL-10 impedes mechanisms of endothelial dysfunction during diabetes. Restoration of vasorelaxation with PEG-SOD or allopurinol suggests that the mechanism(s) by which IL-10 preserves endothelium-dependent vasorelaxation involves O2-, perhaps by reducing production of O2- by xanthine oxidase.
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