Increased lipopolysaccharide-induced tumour necrosis factor levels and death in hypercholesterolaemic rabbits

Nutritional-induced hypercholesterolaemia in New Zealand rabbits causes increased susceptibility to experimental infections. Rabbits fed cholesterol (0.5 g%) for 8 weeks were injected intravenously with varying doses of Escherichia coli 0127: B8 lipopolysaccharide (LPS; 3-100 micrograms/kg). The levels of cholesterol, triglycerides, tumour necrosis factor (TNF), and the survival rates of treated rabbits were then measured. Rabbits fed either normal chow or chow impregnated with sesame oil were used as controls. LPS induced higher serum TNF levels in hypercholesterolaemic rabbits than in normal rabbits or rabbits fed with chow containing sesame oil. TNF levels rose faster in hypercholesterolaemic rabbits than in normal rabbits, reaching maximum levels at 60 min and 120 min, respectively, after LPS injection. The survival rate of hypercholesterolaemic rabbits (1/11) was lower than in normal rabbits (6/7) or rabbits fed with the sesame oil chow (4/4) at the higher LPS doses. No death occurred at lower doses. One possible interpretation of these results, also supported by neutralization experiments, is that increased TNF secretion in hypercholesterolaemic rabbits raises the host's susceptibility to experimental endotoxaemia and possibly to Gram-negative infection.