Transforming growth factor-beta(1) is a potent inhibitor of interleukin-1 beta action in whole ovarian dispersates

Transforming growth factor beta(1) (TGF beta(1)) acts as an inhibitor of th e actions of interleukin-1 beta (IL-1 beta) in various organ systems. In or der better to understand the inter-actions between these polypeptides in th e ovary, we evaluated the effect of TGF beta(1), co-treatment on various IL -1 beta-mediated actions in cultures of whole ovarian dispersates. Treatmen t with IL-1 beta enhanced media accumulation of nitrites (4.8-fold), prosta glandin E-2 (PGE(2), 3.9-fold) and lactate (2.0-fold), and enhanced glucose consumption (2.1-fold). Treatment with TGF beta(1) alone did not significa ntly affect any of these parameters. However, the addition of TGF beta(1) i nhibited IL-1 beta-stimulated nitrite (100%), PGE(2) (44%) and lactate (78% ) accumulation and inhibited IL-1 beta-stimulated glucose consumption (74%) in a dose-dependent manner. The addition of TGF beta(1) also suppressed th e steady-state levels of IL-1 beta-stimulated IL-1 beta, type: I IL-1 recep tor and IL-1 receptor antagonist transcripts (98, 67 and 83% inhibition res pectively). These data suggest that TGF beta(1) is capable of inhibiting se veral IL-1 beta-stimulated endpoints. Since IL-1 has been identified as a p ossible proinflammatory mediator of ovulation and TGF beta has been implica ted as a promotor of fibrosis and healing, we speculate that IL-1 and TGFP might play antagonistic roles in tht normal ovulatory sequence.