Development changes in the febrile response to endotoxin in rabbit

The pyrogenicity of E. coli endotoxin (lipopolysaccharide, LPS) was measured at both 25 degrees C and neutral temperatures (Tn) in day -1 to adult rabbits. Intravenous injection of endotoxin (0.5 micrograms/kg) produced febrile response at Tn in day -1 rabbits, but not at 25 degrees C. A similar response was observed when endotoxin was injected s.c. (1.0 micrograms/kg) or intracisternally (0.0001 micrograms/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. Thus, pyrogenic sensitivity is apparent even in day -1 rabbits. The mechanism of the heat production underlying endotoxin-fever gradually shifted from the nonshivering thermogenesis mediated by catecholamines to shivering thermogenesis during the first month of life.