Transforming growth factor-β₁ is a potent inhibitor of interleukin- 1β action in whole ovarian dispersates

Transforming growth factor β₁ (TGFβ₁) acts as an inhibitor of the actions of interleukin-1β (IL-1β) in various organ systems. In order better to understand the inter-actions between these polypeptides in the ovary, we evaluated the effect of TGFβ₁ co-treatment on various IL-1β-mediated actions in cultures of whole ovarian dispersates. Treatment with IL-1β enhanced media accumulation of nitrites (4.8-fold), prostaglandin E₂ (PGE₂, 3.9-fold) and lactate (2.0-fold), and enhanced glucose consumption (2-1- fold). Treatment with TGFβ₁ alone did not significantly affect any of these parameters. However, the addition of TGFβ₁ inhibited IL-1β-stimulated nitrite (100%), PGE₂ (44%) and lactate (78%) accumulation and inhibited IL- 1β-stimulated glucose consumption (74%) in a dose-dependent manner. The addition of TGFβ₁ also suppressed the steady-state levels of IL-1β- stimulated IL-1β, type I IL-1 receptor and IL-1 receptor antagonist transcripts (98, 67 and 83% inhibition respectively). These data suggest that TGFβ₁ is capable of inhibiting several IL-1β-stimulated endpoints. Since IL-1 has been identified as a possible proinflammatory mediator of ovulation and TGFβ has been implicated as a promotor of fibrosis and healing, we speculate that IL-1 and TGFβ might play antagonistic roles in the normal ovulatory sequence.