Proatherogenic effect of interleukin-18 is exerted with high-fat diet,but not with normal diet in spontaneously hyperlipidemic mice

Aim: it has been considered that interleukin (il)-18,a t helper 1(th1) type cytokine,has a promoting effect on atherosclerosis development. a previous mouse study demonstrated that short-term exogenous il-18 promoted atherosclerosis through a th1 type immune response; however,the serum il-18 may have increased greatly beyond its physiological range,and the effect of increased serum il-18 on atherosclerosis development has not been investigated under different conditions of dietary fat content. the purpose of this study was to reveal the effect of increased serum il-18 within its physiological fluctuations on atherosclerosis development under different conditions of dietary fat content. methods: spontaneously hyperlipidemic (shl) mice were systemically supplied with il-18 for 10 weeks by means of an in vivo gene transfer system with a high-fat diet containing 0.15% cholesterol or a normal diet. results: serum il-18 steadily elevated within its physiological fluctuations. an atherosclerotic lesion area in the aortic root significantly increased with a high-fat diet. systemic cytokine balance shifted to a th1-dominant state,and il-12 mrna in the arterial wall significantly increased with a high-fat diet; however,these findings were not observed with a normal diet. conclusions: it was suggested that the proatherogenic effect of il-18 is physiologically exerted exclusively with a high-fat diet through th1 type immune responses,but not with a normal diet.