Effect of age on fever response to recombinant tumor necrosis factor alpha in a murine model

Certain elderly humans show a blunted fever response to infection. A study was designed using a murine model to assess the influence of age on the febrile response to the endogenous pyrogen, tumor necrosis factor alpha (TNF alpha). Twenty (10 young: 4-6 months; 10 old: 24-28 months) BALB/c mice were injected with 50 ng of TNF alpha into the intraperitoneal space; the experiments were repeated one week later with 100 ng TNF alpha. Control animals received intraperitoneal injections of pyrogen-free phosphate buffered saline. Temperatures were measured rectally at baseline and at 10-minute intervals for 90 minutes post-injection using a thermistor probe and temperature gauge. In the majority of the time intervals following injection, the mean temperature changes of young mice were significantly higher than old mice for both 50 ng and 100 ng doses of TNF alpha. Similarly, peak temperature changes from baseline were consistently higher in young animals following injection of TNF alpha. Moreover, the peak temperature changes in young mice after 50 ng TNF alpha injection were significantly higher than those in old mice following a 100 ng injection of TNF alpha. These findings confirm that (a) TNF alpha has a role in the pathogenesis of fever; (b) aging alters significantly the febrile response; and (c) a mechanism of this age-related blunted febrile response may involve TNF alpha.