TUMOR-NECROSIS-FACTOR-ALPHA INHIBITS IN-VITRO DECIDUALIZATION OF HUMAN ENDOMETRIAL STROMAL CELLS

Interleukin-1 (IL-1) has been reported previously to inhibit the in-vitro deciduaIization of human endometrial stromal cells as assessed by progesterone-induced prolactin production and morphological transformation. In this study we examined whether other cytokines, such as tumour necrosis factor-alpha (TNF alpha), interferon-beta (IFN beta), IFN gamma or granulocyte-macrophage colony-stimulating factor (GM-CSF), could affect the decidualization of human endometrial stromal cells in vitro. Of these cytokines, TNF alpha significantly suppressed prolactin production in a dose-dependent manner, with no apparent effect on cell number, The morphological transformation of endometrial stromal cells was also inhibited by TNF alpha. TNF alpha and IL-1 significantly suppressed cAMP-stimulated prolactin production by endometrial stromal cells, Neither the progesterone concentration in the supernatant of the endometrial stromal cell culture system nor intracellular calcium concentration of the endometrial stromal cells were affected by the addition of TNF alpha or IL-1. These results indicated that TNF alpha and IL-1 suppress both progesterone-induced and cAMP-mediated prolactin production in endometrial stromal cells, and that this inhibition was not attributable to direct effects on progesterone metabolism or related to Ca2+-mediated signal transduction. These experiments suggested that a local increase of TNF alpha and IL-I under certain pathological conditions in vivo may disturb blastocyst implantation and/or the maintenance of pregnancy by inhibiting the decidualization of endometrial stromal cells.