INTERLEUKIN-1-BETA INHIBITS LUTEINIZING HORMONE-INDUCED PLASMINOGEN-ACTIVATOR ACTIVITY IN RAT PREOVULATORY FOLLICLES IN-VITRO

The effects of interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF alpha) on ovulation-associated plasminogen (PA) activity were investigated using preovulatory follicles excised 48 h after equine chorionic gonadotrophin (16IU)-priming of immature rats. Follicles were incubated for 6 and 14 h with a single dose of LH (1 mu g/ml) only, or various cytokine doses in the presence or absence of LH. PA activity in follicular homogenates was determined by a radioactively labelled fibrin-coated plate method and secreted levels of the ovulatory mediators progesterone (P) and prostaglandin E (PGE) were measured by radioimmunoassay. LH induced time-dependent rises in PA (2.5-fold over control at 6 h and fourfold over control at 14 h), while IL-1 beta and TNF alpha alone had no effect over either time period. LH and cytokine coincubations over 14 h revealed that IL-1 beta dose-dependently inhibited the LH-induced increase in PA activity, up to 85%. The effects of TNF alpha on LH-induced PA activity were not significant. Both IL-1 beta and TNF alpha increased P and PGE secretion time- and dose-dependently. In summary, IL-1 beta dose-dependently inhibits the LH-induced increase in PA activity in rat preovulatory follicles in vitro while, as with TNF alpha, increasing P and PGE synthesis. This study, shows that the earlier reported proovulatory action of IL-1 beta is not likely to be mediated by activation of the PA-system and suggests that IL-1 beta may mediate a regulatory loop controlling the extent and distribution of LH-induced PA activity in rat preovulatory follicles.