Interleukin (IL)-4 deficiency does not influence fatty streak formation inC57BL/6 mice

Abundant data is present to implicate oxidatively modified low-density lipo protein (oxLDL) in enhanced atherogenesis. Among the factors involved in LD L oxidation, an important role has been attributed to human 15-lipoxygenase (LO) and its murine analog 12-LO. The expression of these peroxidizing enz ymes is under the control of cytokines, the principal of which is IL-4. In the present study we tested the hypothesis that knocking out the IL-4 gene from C57BL/6 mice would result in suppression of fatty streaks. For this pu rpose, we have fed 45 female IL-4 transgenic knockout (IL-4T KO) and 45 wil d-type (WT) mice an atherogenic diet for 15 weeks. Consecutive determinatio ns of the lipid profile from both study groups were performed at monthly in tervals, and fatty streak formation was assessed at the aortic sinus level, upon sacrifice. The two study groups did not differ significantly with res pect to the lipid profile or the uptake and degradation of iodinated oxLDL by their peritoneal macrophages. We found that the endogenous deficiency of IL-4 did not confer protection from early atherosclerosis in the IL-4T KO as compared to their WT littermates (determined at the aortic sinus). Immun ohistochemical studies, Western blots and 12/15-LO activity assays revealed the presence and activity of 12/15-LO in macrophages of WT mice as well as in IL-4T KO mice. Both did not differ significantly between the study grou ps. The data from this study imply that deficiency in IL-4 does not affect early atherosclerosis in C57BL/6 mice fed a high-cholesterol diet. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.