Stress exacerbates age-related decrements in the immune response to an experimental influenza viral infection

To test the hypothesis that stress exacerbates immune decrements associated with aging, the impact of restraint stress on immunosenescence was assessed using an experimental model of influenza A/Puerto Rico/8/34 viral infection. Beginning one day prior to infection, male C57BL/6 mice, 3 and 22 months of age, were subjected nightly to 12 hours of restraint stress. In both age groups, restraint induced a comparable increase in serum corticosterone levels. However, in contrast to the 3-month-old controls, serum corticosterone levels in 22-month-old mice returned to baseline slower after removal of the stressor. The characteristic influenza-driven increase in cellularity of the lung and draining lymph node was decreased by age and further suppressed by stress. Natural killer cell activity and virus-specific T helper cell function were also blunted by age and almost completely abrogated by stress. Furthermore, due to the weak immune response to viral infection, aged animals subjected to stress had a lower survival rate than age-matched controls.