IL-10 deficiency increases superoxide and endothelial dysfunction during inflammation

Little is known about the role of interleukin-10 (IL-10), an antiinflammato ry cytokine, in blood vessels. We used IL-10-deficient mice (IL-10 -/-) to examine the hypothesis that IL-10 protects endothelial function after lipop olysaccharide (LPS) treatment. The responses of carotid arteries were studi ed in vitro 6 h after injection of a relatively low dose of LPS (10 mu g ip ). In IL-10 -/- mice, the maximum relaxation to ACh (3 mu M) was 56 +/- 6% (means +/- SE) after LPS injection and 84 +/- 4% after vehicle injection (P < 0.05). Thus endothelium-dependent relaxation was impaired in carotid arte ries from IL-10 -/- mice after LPS injection. In contrast, this dose of LPS did not alter relaxation to ACh in vessels from wild-type (IL-10 +/+) mice . Relaxation to nitroprusside and papaverine was similar in arteries from b oth IL-10 -/- and IL-10 +/+ mice after vehicle or LPS injection. Because in flammation is associated with increased levels of reactive oxygen species, we also tested the hypothesis that superoxide contributes to the impairment of endothelial function by LPS in the absence of IL-10. Results using conf ocal microscopy and hydroethidine indicated that levels of superoxide are e levated in carotid arteries from IL-10 -/- mice compared with IL-10 +/+ mic e after LPS injection. The impaired relaxation of arteries from IL-10 -/- m ice after LPS injection was restored to normal by polyethylene glycol-suspe nded superoxide dismutase (50 U/ml) or allopurinol (1 mM), an inhibitor of xanthine oxidase. These data provide direct evidence that IL-10 protects en dothelial function after an acute inflammatory stimulus by limiting local i ncreases in superoxide. The source of superoxide in this model may be xanth ine oxidase.