Suppression of experimental atherosclerosis in rabbits by interferon-inducing agents

The effects of two chemically different interferon inducers on the suppression of atherosclerosis were studied in rabbits fed an atherogenic chow diet. One group (10 rabbits per group) was fed normal rabbit chow, and three groups were fed an atherogenic chow. One of the latter groups received the atherogenic feeding alone; the other two were treated with either polyinosinic-polycytidylic acid (poly I:C) or 2-amino-5-bromo-6-phenyl-4-pyrimidinone (ABPP). Neither of the drugs reduced significantly the hypercholesterolemia induced by the feeding. However, both poly I:C and ABPP treatment significantly reduced the percent area of the aortic intimal surface lesions, stained for lipid with Sudan IV, compared with that in untreated rabbits fed atherogenic chow. Microscopic sections of typical aortic plaques showed that both drug treatments significantly reduced the size and number of intimal lipid deposits compared with those observed in the aortas of untreated animals. Chemical analysis for cholesterol and collagen content revealed that interferon-inducing agents significantly reduced cholesterol deposits in the aorta, with little effect on fibrous protein deposition. The results indicate that two unrelated interferon-inducing drugs suppressed atherogenesis without reducing serum cholesterol and low density lipoprotein levels. Whether the protection against atherosclerosis is exerted by endogenous interferon production remains to be determined.