INCREASED LIPOPOLYSACCHARIDE-INDUCED TUMOR-NECROSIS-FACTOR LEVELS ANDDEATH IN HYPERCHOLESTEROLEMIC RABBITS

Nutritional-induced hypercholesterolaemia in New Zealand rabbits cause s increased susceptibility to experimental infections. Rabbits fed cho lesterol (0.5 g%) for 8 weeks were injected intravenously with varying doses of Escherichia coli 0127 : B8 lipopolysaccharide (LPS 3-100 mu g/kg). The levels of cholesterol, triglycerides, tumour necrosis facto r (TNF), and the survival rates of treated rabbits were then measured. Rabbits fed either normal chow or chow impregnated with sesame oil we re used as controls. LPS induced higher serum TNF levels in hyperchole sterolaemic rabbits than in normal rabbits or rabbits fed with chow co ntaining sesame oil. TNF levels rose faster in hypercholesterolaemic r abbits than in normal rabbits, reaching maximum levels at 60 min and 1 20 min, respectively, after LPS injection. The survival rate of hyperc holesterolaemic 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 thes e results, also supported by neutralization experiments, is that incre ased TNF secretion in hypercholesterolaemic rabbits raises the host's susceptibility to experimental endotoxaemia and possibly to Gramnegati ve infection.