Effect of physical stress on sensitivity of lymphocytes to inhibition by prostaglandin E ₂

Physical stress is associated with depressed cellular immune function. We have found that lymphocytes from subjects undergoing either of 2 stressful events, cardiac surgery or childbirth, are more sensitive to inhibition by PGE ₂. For example, the concentration of PGE ₂ required for 50% inhibition of ³H-thymidine incorporation (ID ₅₀) into phytohemagglutinin-stimulated lymphocytes from patients undergoing cardiac surgery went from 1.5x10 ^-8 M on the day before surgery to 3x10 ^-9 M on the day after surgery. This increase in sensitivity to PGE ₂ was accompanied by a significantly decreased lymphocyte proliferative response (27 to 68% of control, depending on mitogen dose) and a 50% increase in the percentage of E rosette-positive cells with receptors for the Fc portion of IgG. The increased sensitivity to PGE the Fc portion of IgG. The increased sensitivity to PGE and the depressed mitogen responses returned to preoperative values by day 10. The depressed mitogen responses of the postoperative patients were completely restored to normal by removal of glass-adherent cells before culture. In addition, the responses of the postoperative patients and the women in labor were partially restored by the addition of indomethacin, a prostaglandin synthetase inhibitor, to the cultures. Thus it would appear that physical stress causes lymphocytes to become more sensitive to prostaglandin E ₂, and the increased sensitivity to inhibition by this immunomodulator is responsible in part for the depressed cellular immune function after physical stress.