INTERLEUKIN-1 INHIBITS THE OVARIAN STEROID-INDUCED LUTEINIZING-HORMONE SURGE AND RELEASE OF HYPOTHALAMIC LUTEINIZING-HORMONE-RELEASING HORMONE IN RATS

Interleukin-1 (IL-1), a polypeptide cytokine secreted by activated macrophages, has been postulated as a chemical messenger between the immune and endocrine systems. IL-1-immunopositive neurons and fibers have been visualized in the human and rat hypothalamus, and IL-1 receptors are present in the rat brain. We have examined the effects of human recombinant IL-1 (α - and β-subtypes) on LH release in vivo and hypothalamic LHRH release in vitro. Ovariectomized rats were primed with estradiol benzoate, and progesterone was injected 48 h later to elicit a LH surge in the afternoon. IL-lα and IL-1β were injected either intracerebroventricularly (icv) via a preimplanted cannula in the third ventricle of the brain or iv. Systemic injection of IL-la or IL-lβ (58.8 pmol at 1300 and 1500 h) failed to influence the afternoon LH surge seen in saline-injected control rats. However, IL-lβ (1.76 pmol) administered icv at 1300 and 1500 h or a single icv injection at 1300 h blocked the progesterone-induced LH surge. Similar icv injections of ILlα also significantly suppressed the afternoon LH surge compared to that in saline-injected control rats. However, IL-lα was relatively less effective than the β-subtype, since the LH surge was detected in some rats. To ascertain whether suppression of the LH surge was due to inhibition of LHRH release, the medial basal hypothalamus-preoptic area of estradiol benzoate-progesterone-treated ovariectomized rats was incubated with and without IL-1. Both IL-lα and IL-lβ, at concentrations of 0.1 nM and higher, significantly suppressed LHRH release in vitro from the medial basal hypothalamus-preoptic area. In contrast, IL-1 (10 nM) was completely ineffective in suppressing LHRH release from the microdissected median eminence. These results demonstrated an overall inhibitory effect of icv IL-1 on the LHRH-LH axis and suggest that suppression of the steroid-induced LH surge by IL-1 may primarily be due to inhibition of LHRH release at hypothalamic sites located within the blood-brain barrier. © 1990 by The Endocrine Society.