Changes in lymphocyte sensitivity to prostaglandin E, histamine, hydrocortisone, and X irradiation with age: Studies in a healthy elderly population

The sensitivity to the endogenous immunomodulators prostaglandin E, histamine, and hydrocortisone, as well as to X irradiation, was studied in mitogen-stimulated lymphocytes from old and young donors. The subjects included 279 healthy individuals over age 65, 24 "chronically ill" elderly individuals living in the community, 25 nursing home in-patients, and 180 healthy young controls. We confirmed our earlier finding of an increase in sensitivity to inhibition by PGE in healthy elderly individuals. The ID₅₀ for PGE₂ for the 279 individuals over 65 was 2.7 (± 0.2) × 10^-8 M versus 4.6 (± 0.3) × 10^-7 M for the 180 young controls (mean ± SEM, P < 0.0001). While the mean PHA responses of the healthy elderly individuals were not different from the responses of the chronically ill or nursing home populations, lymphocytes from these latter two groups were significantly less sensitive to PGE₂. The more sensitive a healthy elderly subject's lymphocytes were to PGE₂, the lower was the initial PHA response (r = 0.43, P < 0.0001). Exposure to 100 or 500 rad of X irradiation prior to culture caused significantly more inhibition of [³H]thymidine incorporation into lymphocytes from healthy old people than into lymphocytes from young controls. On the other hand, lymphocytes from healthy elderly individuals were significantly less sensitive to inhibition by hydrocortisone (P < 0.001 at each of three hydrocortisone concentrations). The lowest dose of hydrocortisone (10^-8 M) actually enhanced [³H]thymidine incorporation in lymphocytes of 30% of old people but not in young people (P < 0.001 by χ²). Lymphocytes from old people were also less sensitive to inhibition by histamine (20 ± 4% inhibition by 10^-5 M histamine in lymphocytes from old people versus 41 ± 2% inhibition in young people, P < 0.0001). Thus, while there are substantial changes with age in sensitivity to several different immunomodulators, the direction of the change in sensitivity varies depending on the agent.