Synergistic effect of progesterone on prostaglandin E modulation of the mitogenic response of human peripheral lymphocytes.
The combined effects of prostaglandins of the E series (PGE) and progesterone (P), both of which are found to increase locally in the secretory endometrium, were studied in mitogen-stimulated cultures of lymphocytes from human peripheral blood. When added separately to lymphocyte cultures, both PGE and P produced a concentration-dependent inhibition of T-cell, but not B-cell, mitogenesis. If added together, these agents caused a much greater inhibition of T-cell mitogenesis, with marked synergy, than that observed with either agent alone. The synergistic inhibition was achieved with endometrial concentrations of PGE and P. The kinetics of PGE- and P-mediated inhibition investigated at various times during lymphocyte activation indicated that both agents affected the early events of T-cell mitogenesis. PGE- and P-inhibition of T-cell mitogenesis were shown to be reversible phenomena by washing the cells treated with these agents. These results suggest that elevated levels of PGE and P in the secretory endometrium, acting synergistically in inhibiting the proliferative response of T cells, may participate in facilitating implantation of histoincompatible fetal tissue in the maternal uterus as non-specific local immunosuppressive factors.
D000328:Adult; D004357:Drug Synergism; D004717:Endometrium / Q000276:immunology / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007166:Immunosuppressive Agents; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects*; D008934:Mitogens / Q000494:pharmacology; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology*; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology
D007166:Immunosuppressive Agents; D008934:Mitogens; D011459:Prostaglandins E, Synthetic; D011374:Progesterone