Effect of age on fever and acute-phase response of rats to endotoxin and Salmonella typhimurium.

Age-related effects on endogenous pyrogen-mediated febrile and acute-phase responses to endotoxin and Salmonella typhimurium challenge were investigated in young adult and aged Fisher 344 rats. After injection of endotoxin, the febrile response over 6 h and the fall in plasma iron and zinc after 6 h were determined in 14 young adult and 14 aged rats in their thermoneutral zone (26 degrees C) and in 14 young adult and 14 aged rats maintained in a cold environment (15 degrees C). Although at 26 degrees C aged rats showed only a slightly diminished febrile response compared with that of young adult rats, at 15 degrees C they had a markedly diminished febrile response compared with that of young adult rats. At both 26 and 15 degrees C, the injection of endotoxin led to a fall in iron and zinc concentrations in the plasma of both young adult and aged rats. The intact trace metal response diminished but febrile response suggest that aged rats are able to produce endogenous pyrogen but have a reduced capacity to respond to this substance. In 22 aged and 22 young adult rats maintained at 26 degrees C and challenged with S. typhimurium, the febrile response was significantly less in the aged rats but the survival rate was virtually identical. When 10 young adult and 10 aged rats were placed at a temperature of 15 degrees C after injection with S. typhimurium, the febrile response in the aged rats was significantly lower than that in the young adult rats at only one time point, and the survival rate did not differ between the two age groups. Survival after challenge with S. typhimurium was not influenced adversely by the diminished febrile response.