Modulation of the mitogenic response of lymphocytes from young and aged individuals by prostaglandins and indomethacin

The effect of indomethacin (IND) on the mitogenic responses of human peripheral blood lymphocytes was dependent upon the dose of mitogen employed; in contrast, the effect of prostaglandins (PGs) was independent of the mitogen dose. When a single concentration of mitogen was used to study the effect of IND on blastogenesis, extremely variable results were observed, even among a healthy population group. This variability within the group was reduced to a minimum when mitogen dose-response studies were performed with and without IND and maximal blastogenic responses were compared. Employing such acriterion, no age-related differences were noted on addition of IND. Kinetic experiments revealed that significant quantities of PGs must be present very early during the culture period to influence the lectin-induced mitogenesis. These findings, together with recently published data from other laboratories, lead us to conclude that endogenously synthesized PGs may not be able to influence the lectin-induced mitogenic process. The effect of IND observed at submitogenic doses of lectins may be due to other pharmacological actions such as its effect on cyclic AMP-dependent protein kinases.