PROGESTERONE CONTROL OF INTERLEUKIN-8 PRODUCTION IN ENDOMETRIUM AND CHORIO-DECIDUAL CELLS UNDERLINES THE ROLE OF THE NEUTROPHIL IN MENSTRUATION AND PARTURITION

Interleukin-8 (IL-8) attracts neutrophils into tissues and causes them to degranulate. Both menstruation and parturition involve neutrophil migration into uterine tissues and therefore IL-8 is a likely mediator of the tissue re-arrangements that accompany these events. We have ex amined the ability of endometriun explants and chorion cells in cultur e to synthesize and release IL-8 and the ability of progesterone, a sy nthetic progestin [medroxyprogesterone acetate (MPA)] and dexamethason e to inhibit this production. In endometrium, the stage of the menstru al cycle did not affect IL-8 production but a 10(-6) M concentration o f progesterone or dexamethasone significantly reduced the concentratio n of IL-8 in medium after 24 h. After a further 24 h with lipopolysacc haride (LPS) stimulation, only MPA and dexamethasone inhibited product ion significantly. In chorion cells, IL-8 production was significantly decreased by both MPA and dexamethasone in the LPS stimulated cells b ut the reduction in the first 24 h was not significant. The IL-8 produ ced in uterine tissues might act synergistically with prostaglandin E (PGE), a likely site for this interaction being blood vessels where PG E production is also repressed by progesterone. Such a cooperative act ion would maintain low leukocyte entry into uterine tissues in the pre sence of progesterone and falling steroid levels would induce leukocyt e immigration and activation with consequent tissue destruction. Such steroid-dependent interactions are important in our understanding of t he mechanisms of menstruation and parturition and could allow new appr oaches to the treatment of uterine pathology.