Sensitivity of lymphocytes to prostaglandin E₂ increases in subjects over age 70

We examined the sensitivity of lymphocytes from different age groups to inhibition by prostaglandin E₂. Phytohemagglutinin-stimulated cultures of peripheral blood mononuclear cells from 12 healthy subjects over the age of 70 were much more sensitive to inhibition by exogenously added prostaglandin E₂ than were cells from 17 young controls (ID⁵⁰ ≃ 10 nM for the subjects over 70 vs. > 3 μM for the young controls). The more sensitive lymphocytes from a subject over 70 were to prostaglandin E₂, the lower was his or her response to phytohemagglutinin (r = 0.75, P < 0.01). The mean responses to phytohemagglutinin of the peripheral blood mononuclear cells from the subjects over 70 were significantly depressed compared to the young controls. Addition of indomethacin, a prostaglandin synthetase inhibitor, to the cultures resulted in an increase in [³H]thymidine incorporation of 140 ± 16% in the cells of the subjects over 70 vs. a 36 ± 3% increase in the young controls (mean ± SEM, P < 0.001). The mean phytohemagglutinin response of the subjects over 70 was 40% of the control response without indomethacin. With addition of indomethacin the response of subjects over 70 rose to 72% of control. Thus, increased sensitivity to prostaglandin E₂ appears to be responsible in part for the depressed mitogen response of peripheral blood mononuclear cells from healthy subjects over 70.