Cyclosporin A inhibits prostaglandin E(2) production by fetal amnion cells in response to various stimuli

Use of cyclosporin A as part of an immunosuppressive regimen in pregnant transplant patients is not uncommon. Although successful pregnancies have been reported with the use of various immunosuppressive agents including cyclosporin A, the concern for fetal outcome still remains. Our purpose was to evaluate the effects of immunosuppressive cyclosporin A on prostaglandin E(2) (PGE(2)) production by human fetal amnion. Amnion cells were isolated from term placentae obtained at elective cesarean section before the onset of labor. Cells were grown to confluence and then incubated for 16 hours with cyclosporin A (1-1000 ng/ml) in the presence and absence of interleukin 1 beta (IL-1 beta, 1 ng/ml), phorbol 12-myristate 13-acetate (PMA, 10(-7) M) and ionomycin (0.5 mu M). PGE(2) was measured by radioimmunoassay and cellular protein determined. IL-1 beta, PMA and ionomycin all stimulated amnion cell PGE(2) production as expected. However, these stimulatory actions were attenuated by at least 50% when cells were co-incubated with cyclosporin A (1000 ng/ml). Concentrations of cyclosporin A tested included the therapeutic range (250-1000 ng/ml). Our results indicate that cyclosporin A does not stimulate amnion cell PGE(2) production and is probably unrelated to preterm labor and delivery in allograft recipients.