Dietary hepatic cholesterol elevation: effects on coxsackievirus B infection and inflammation

Abstract

Mice made hypercholesterolemic (HC) by diet are highly susceptible to coxsackievirus (CV) B5, whereas normal adult animals remain resistant. In attempting to define those dietary-induced physiological changes which contribute to altered resistance, a strong association between accumulation of intrahepatic cholesterol and increased CV B5-induced mortality was demonstrated, with maximum susceptibility to CV coinciding with a 2.5-fold increase in the ratio of hepatic cholesterol to protein. This metabolic imbalance was associated with a lower clearance rate of CV from the blood and liver of C57BL/6 mice, although virus-specific neutralizing antibody production was unaltered. In addition to CV, HC mice were more susceptible to an intravenous inoculation of Listeria monocytogenes in comparison to controls. The macrophage stimulant Corynebacterium parvum failed to increase resistance of HC mice to a high dose of CV B4 and L. monocytogenes and failed to induce the hepatomegaly, splenomegaly, and cellular infiltrate seen in the liver and spleen of normal animals. Furthermore, the peritoneal monocytic infiltrate induced by thioglycolate in normal animals was absent in HC mice. Results from these experiments suggest that decreased resistance to CV in the HC host is attributed to a defect in the nonspecific immune responses of macrophages and monocytes which are of primary importance in resistance to this virus and other infectious agents.