Fever and aging: central nervous system prostaglandin E2 in response to endotoxin

The pathophysiology of the blunted febrile response often seen in elderly individuals with infection is not well understood. In this study, we attempted to determine the impact of aging on prostaglandin E2 release from the brain in response to endotoxin (LPS) stimulation. Eight young (4-6 month) and eight old (24-28 month) BALB/c mice were studied. Right and left half brains from old and young mice were either stimulated with LPS or control solution. Each mouse provided a stimulated and a control value. Results were reported for each mouse as the difference (stimulated minus control) in picograms of PGE2 released per milligram tissue and as the percent of baseline (control). Significant stimulation was demonstrated in the young mice, mean difference being +3.7 pg/mg, SD = 2.2 (Student's paired t, p less than 0.01) or +44% of control. In the old mice the mean difference was +2.9 pg/ml, SD = 6.7, or +22%, which was not statistically significant. Moreover, in three of eight old mice, there was a lack of PGE2 stimulation. The authors conclude that in a select group of old mice ("nonresponders"), the failure to mount a febrile response to an infection may be related to diminished release of PGE2 from the brain.