Evidence that the interleukin-1 beta-induced prostaglandin E2 release from rat hypothalamus is mediated by type I and type II interleukin-1 receptors.

Interleukin-1 beta (IL-1 beta) has been shown to specifically increase the release of prostaglandin (PG) E2 from rat hypothalamic explants in short-term experiments. In this study we attempted to characterize the receptor subtype(s) involved in this response. Rat hypothalamic explants were incubated with mouse monoclonal antibodies (mAbs) raised against human IL-1 type I or type II receptors, IL-1 receptor antagonist (IL-1ra) and alpha-melanocyte-stimulating hormone (alpha-MSH) (which appears to antagonize certain IL-1 induced inflammatory effects in vivo), alone and in the presence of IL-1 beta. PGE2 released into the incubation medium was measured by radioimmunoassay. The anti-type I mAb reduced both basal and IL-1 beta-stimulated PGE2 release at 10 micrograms/ml, but not at lower concentrations. The anti-type II mAb also produced a significant decrease in stimulated release but had no effect on basal release. IL-1ra mimicked the effects of the anti-type I mAb, while alpha-MSH failed to alter either basal or stimulated PGE2 release. These findings suggest that IL-1 beta controls production and release of PGE2 by the rat hypothalamus via both type I and type II receptors, although the latter appear to be involved only in the response to high levels of IL-1.