Interleukin-1β Stimulates Progesterone Production byin VitroHuman Luteal Cells: Evidence of a Mediatory Role of Prostaglandins

We have investigated whether IL-1 beta, a cytokine with an important role in ovarian physiology, is also involved in progesterone (P) synthesis in human luteal cells, and whether this effect is mediated via the cyclooxygenase (COX) pathway. Human luteal cells were cultured for 24 h in the presence of IL-1 beta (0.01-10 ng/ml), given alone or in combination with human chorionic gonadotropin (100 ng/ml), indomethacin (1 micro g/ml), or P (100 ng/ml). We observed a significant increase in prostaglandin (PG)release after IL-1 beta treatment; the cytokine was more effective on PGE(2) than PGF(2 alpha) release. The effect of IL-1 beta was abolished by human chorionic gonadotropin, which had no action on basal PG levels when given alone; in contrast, P reduced basal, but not IL-1 beta-stimulated, PG production. Treatment with the human IL-1 receptor antagonist was associated with a decrease in both basal and IL-1 beta-stimulated PG production. Moreover, IL-1 beta induced a concentration-dependent increase in P production and release, an effect counteracted by the COX inhibitor indomethacin. In conclusion, our data show the ability of IL-1 beta to influence P secretion via the COX pathway, thereby suggesting a possible luteotropic role in human ovary based on an autocrine-paracrine mechanism.