The immunoregulatory effect of endogenous prostaglandin E2 (PGE2) on immunoglobulin production was studied in an in vitro culture system of human peripheral blood mononuclear cells, stimulated with pokeweed mitogen (PWM). Three different cyclooxygenase inhibitors (indomethacin, carprofen, and piroxicam) suppressed Ig synthesis by ~50%. This inhibitory effect could be reversed by adding low doses of exogenous PGE2 (3 × 10-9 to 3 × 10-8M). These doses are endogenously produced in PWM-stimulated cultures, and a concentration of 2 × 10-8M is reached after 48 hr of culture. When B cells were directly stimulated with helper factor, PGE2 did not enhance Ig production and doses of 3 × 10-7M to 3 × 10-6M were inhibitory. The effects of indomethacin and PGE2 were eliminated when T cells were irradiated or treated with mitomycin prior to culture. The enhancing effects of PGE2 were substantially reduced after OKT8(+) T cells were removed from the system. PWM-stimulated cultures of lymphocytes from healthy subjects over age 70 were more sensitive to inhibition by indomethacin and to stimulation by PGE2 than were cultures of lymphocytes from young controls. Thus the major role of endogenous PGE in polyclonal Ig production in vitro is to tonically inhibit a radiosensitive, OKT8(+) suppressor T cell. This tonic inhibition is increased in subjects over 70, which provides one explanation for decreased suppressor cell function in elderly subjects.
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