IFN-g Deficiency Exerts Gender-Specific Effects on Atherogenesis in Apolipoprotein E2/2 Mice

We have shown recently that administration of exogenous interferon-g (IFN-g) to apolipoprotein E (apoE)2/2 mice augmented atherogenesis. In the present study, we examined whether deficiency of endogenous IFN-g would reduce atherosclerosis in apoE2/2 mice. Compound-deficient mice were generated by crossing strain-matched IFN-g2/2 and apoE2/2 mice and comparing them to apoE2/2 mice. Groups of both genders were fed either a normal or a high-fat diet. IFN-g deficiency did not affect serum cholesterol concentrations or lipoprotein-cholesterol distributions in any groups. IFN-g deficiency had no effect on serum triglyceride con-centrations, except for an increase noted in males fed a normal diet. The extent of atherosclerosis was deter-mined in tissue sections of the ascending aorta and on the surface of the aortic arch. During feeding of nor-mal diets, IFN-g deficiency had no effect on the extent of atherosclerosis in female mice in either vascular bed. In contrast, in male mice fed normal diet, IFN-g deficiency markedly decreased lesion size in both vas-cular beds. During feeding of high-fat diets, IFN-g deficiency also had no effect on lesion size in females but profoundly decreased lesion size in the aortic root of male mice. IFN-g deficiency had no effect on the abun-dance of T lymphocytes or MHC class II-positive cells in aortic root lesions of females. By comparison, both these parameters were reduced in lesions of male mice. Therefore, IFN-g deficiency decreased atherogenesis, potentially by decreasing T lymphocyte presence and cell activation, without influencing serum cholesterol concentrations. However, this effect is strikingly restricted to male mice. 66