Immune tolerance and atherosclerosis in rabbits. Effect of high-fat and cholesterol-supplemented diets.

Breeding rabbits were fed diets supplemented with 5% milk or soya protein for 1 month before conception and throughout pregnancy and lactation. Four groups of 5 or 6 of their offspring were given high-energy isonitrogenous diets containing either 30% soya or milk protein. Half of the animals from each litter received the same protein as their dams; the remainder were fed the alternative (i.e. dams soya; offspring milk, and vice versa). 0.75% cholesterol was added to the diets between 30 and 120 days after weaning. Animals given the same protein as their dams formed substantially lower amounts of food antigen-specific antibody than rabbits fed a novel protein at weaning but the extent of aortic atherosclerosis was similar in all groups. In a second experiment groups of 5-8 weanling rabbits were fed a cholesterol-free diet containing 30% soya and 17% saturated fat for 1 year. Animals in group 1 were bred from dams given soya but those in groups 2 and 3 were derived from a colony fed a soya-free diet. Rabbits in group 3 were immunised by repeated parenteral injections of soya protein and developed high levels of antisoya antibodies. Group 1 and 2 animals were injected with saline only but antisoya antibodies were substantially higher in animals derived from the soya-free breeding colony. Although serum cholesterol and triglyceride levels were similar in all groups, animals from dams fed soya (group 1) had significantly less aortic atherosclerosis (10% involvement of ascending aorta) than those reared from a colony fed a soya-free diet (group 2; 32%). Parenteral immunization with soya protein (group 3) was not associated with significantly increased atherosclerosis (37%). These findings indicate that perinatal exposure to dietary antigen in rabbits may be important in modulating the systemic immune reaction to food antigens. The magnitude of this systemic response is unlikely to alter the nature or distribution of cholesterol-induced atherosclerosis but may have an important influence on the development of aortic disease produced by prolonged feeding of high-fat, cholesterol-free diets.