Interleukin-1β is a potent stimulator of prostaglandin synthesis in bovine luteal cells

Interleukin-1 (IL-1) is a polypeptide that has both local and systemic effects on numerous tissues, including endocrine cells. To evaluate the effect of IL-1 on luteal function, bovine luteal cells were cultured for 5 days with increasing concentrations (0.1, 0.5, 1.0, 2.5, 5.0, 10.0 ng/ml) of recombinant bovine interleukin-1β (rbIL-1β). IL-1β increased the production of luteal 6-keto-prostaglandin-F(1α) (6-keto-PGF(1α)), prostaglandin E₂ (PGE₂), and prostaglandin F(2α) (PGF(2α)) in a dose-dependent manner, but had no effect on progesterone (P₄) production. Treatment with the cyclooxygenase inhibitor, indomethacin (5 μg/ml), inhibited basal, as well as rbIL-1β-stimulated prostaglandin production. Addition of Iloprost (a synthetic analogue of prostacyclin, 5 ng/ml) suppressed basal production of PGF(2α) and PGE₂, but did not reduce the stimulatory effect of rbIL-1β. Similarly, PGF(2α) suppressed basal, but not IL-1β-stimulated, production of 6-keto-PGF(1α). PGE₂ had no effect on the synthesis of either PGF(2α) or 6-keto-PGF(1α). P₄ (1.75 μg/ml) reduced basal as well as rbIL-1β-stimulated production of 6-keto-PGF(1α), PGE₂, and PGF(2α). These results indicate that IL-1β could serve as an endogenous regulator of luteal prostaglandin production. It appears that IL-1β action is not modified by exogenous prostaglandins, but is at least partially regulated by elevated P₄. It is possible that the role of IL-1β in stimulation of luteal prostaglandin production may be confined to a period characterized by low P₄ levels, such as during luteal development or regression.