Development Changes in the Febrile Response to Endotoxin in Rabbit

Abstract

The pyrogenicity of Escherichia coli endotoxin (lipopolysaccharide, LPS) was measured at 25.degree. C and neutral temperatures (Tn) in rabbits of different age. I.v. injection of endotoxin (0.5 .mu.g/kg) produced febrile response at Tn in day 1 [1 day old] rabbits but not at 25.degree. C. A similar response was observed when endotoxin was injected s.c. (1.0 .mu.g/kg) or intracisternally (0.0001 .mu.g/kg). The mean magnitude of the rise of rectal temperature increased with the advance of age. Propranolol abolished the endotoxin-fever in day 3 rabbits. The inhibitory effect of propranolol was incomplete in day 14 rabbits and was not seen in day 28 rabbits. The inhibitory effect of phentolamine was not observed in day 3 and day 28 rabbits but the blocker reduced the febrile response in day 14 rabbits. No shivering activity was evident in day 3 rabbits after injection of endotoxin. In the day 7 and 14 rabbits, shivering was less significant and of shorter duration than in the case of day 28 rabbits. The endotoxin caused no significant decrease in ear skin temperature in day 3 rabbits. A decrease in ear skin temperature was observed in rabbits older than 14 days. Pyrogenic sensitivity is apparent even in day 1 rabbits. The heat production mechanism underlying endotoxin-fever gradually shifted from the nonshivering thermogenesis mediated by catecholamines to shivering thermogenesis during the 1st mo. of life.